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The Role of Autoantibody Testing in Modern Personalized Medicine

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Abstract

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases.

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References

  1. Auffray C, Charron D, Hood L (2010) Predictive, preventive, personalized and participatory medicine: Back to the future. Genome Med 2:57

    Article  Google Scholar 

  2. Yaniv G, Twig G, Shor DB, Furer A, Sherer Y, Mozes O et al (2015) A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients. Autoimmun Rev 14:75–79

    Article  CAS  Google Scholar 

  3. Fava A, Petri M (2019) Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 96:1–13

    Article  Google Scholar 

  4. Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS (2010) Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum 39:257–268

    Article  Google Scholar 

  5. Vilar MJ, Sato EI (2002) Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil). Lupus 11:528–532

    Article  Google Scholar 

  6. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R et al (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 78:1151–1159

    Article  Google Scholar 

  7. Fernandez SA, Lobo AZ, Oliveira ZN, Fukumori LM, Périgo AM, Rivitti EA (2003) Prevalence of antinuclear autoantibodies in the serum of normal blood donors. Rev Hosp Clin Fac Med Sao Paulo. 58:315–319

  8. Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE (2011) Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum 63:191–200

    Article  CAS  Google Scholar 

  9. Dinse GE, Parks CG, Weinberg CR, Co CA, Wilkerson J, Zeldin DC et al (2020) Increasing prevalence of antinuclear antibodies in the United States. Arthritis Rheumatol 72:1026–1035

    Article  CAS  Google Scholar 

  10. Dellavance A, Gabriel AJ, Nuccitelli B, Taliberti T, von Mühlen C, Bichara CDA et al (2009) Third Brazilian consensus for autoantibody research in HEp-2 cells (FAN). Recommendations for standardization of the autoantibody screening assay in HEp-2 cells, quality control and clinical associations. Rev Bras Rheumatol 49:89–109

  11. Damoiseaux J, Andrade LEC, Carballo OG, Conrad K, Francescantonio PLC, Fritzler MJ et al (2019) Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective. Ann Rheum Dis 78:879–889

    Article  CAS  Google Scholar 

  12. Chan EKL, Damoiseaux J, Carballo OG, Conrad K, Cruvinel WM, Francescantonio PLC et al (2015) Report of the first international consensus on standardized nomenclature of antinuclear antibody HEp-2 cell patterns 2014–2015. Front Immunol 6:412

    Article  Google Scholar 

  13. Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT et al (2009) A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 61:1168–1178

    Article  CAS  Google Scholar 

  14. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D et al (2011) A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 63:3918–3930

    Article  CAS  Google Scholar 

  15. Prado MS, Dellavance A, Rodrigues SH, Marvulle V, Andrade LEC (2020) Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus. Clin Chem Lab Med 58:1271–1281

    Article  CAS  Google Scholar 

  16. Choi MY, Clarke AE, St Pierre Y, Hanly JG, Urowitz MB, Romero-Diaz J et al (2018) Antinuclear antibody-negative systemic lupus erythematosus in an international inception cohort. Arthritis Care Res (Hoboken) 71:893–902

  17. Quismorio F, Torralba K (2013) Clinical application of serologic tests, serum protein abnormalities, and other clinical laboratory test in SLE. In: Wallace D, Hahn B (eds) Dubois’ lupus erythematosus and related syndromes, 8th edn. Elsevier Saunders, Philadelphia, PA, pp 526–540

    Chapter  Google Scholar 

  18. Brito-Zerón P, Izmirly P, Ramos-Casals M, Buyon J, Khamashta M (2015) The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol 11:301–312

    Article  Google Scholar 

  19. Wahren-Herlenius M, Sonesson SE, Clowse ME (2012) Neonatal lupus erythematosus. In: Wallace D, Hahn B (eds) Dubois’ lupus erythematosus and related syndromes, 8th edn. Saunders, Philadelphia, pp 464–472

    Google Scholar 

  20. Sammaritano L, Bermas B, Chakravarty E, Chambers C, Clowse M, Lockshin M et al (2020) 2020 American college of rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 72:529–556

    Article  Google Scholar 

  21. Lazzerini PE, Acampa M, Guideri F, Capecchi PL, Campanella V, Morozzi G et al (2004) Prolongation of the corrected QT interval in adult patients with anti-Ro/SSA-positive connective tissue diseases. Arthritis Rheum 50:1248–1252

    Article  Google Scholar 

  22. Lazzerini PE, Capecchi PL, Guideri F, Bellisai F, Selvi E, Acampa M et al (2007) Comparison of frequency of complex ventricular arrhythmias in patients with positive versus negative anti-Ro/SSA and connective tissue disease. Am J Cardiol 100:1029–1034

    Article  Google Scholar 

  23. Satoh M, Fritzler MF, Chan EKL (2020) Antihistone and antispliceosome antibodies. In: Tsokos GC (ed) Lupus erythematosus: basic, applied and clinical aspects, 1st edn. Academic Press, New York, pp 237–247

    Google Scholar 

  24. Furtado R, Pucinelli M, Cristo V, Andrade L, Sato E (2002) Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud’s phenomenon in SLE patients. Lupus 11:35–41

    Article  CAS  Google Scholar 

  25. Migliorini P, Baldini C, Rocchi V, Bombardieri S (2005) Anti-Sm and anti-RNP antibodies. Autoimmunity 38:47–54

    Article  CAS  Google Scholar 

  26. Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I et al (2003) Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: Significant factors associated with lupus nephritis. Ann Rheum Dis 62:556–560

    Article  CAS  Google Scholar 

  27. van Vollenhoven RF, Fly M, Bertsias G, Isenberg D, Kuhn A, Lerstrom K et al (2014) Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 73:958–967

    Article  Google Scholar 

  28. Tseng C, Buyon J, Kim M, Belmont H, Mackay M, Diamond B et al (2006) The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: Findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 54:3623–3632

    Article  CAS  Google Scholar 

  29. Hung W, Chen Y, Lan J, Chen H, Chen Y, Chen D et al (2011) Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis. Lupus 20:1404–1410

    Article  CAS  Google Scholar 

  30. Ng K, Manson J, Rahman A, Isenberg D (2006) Association of antinucleosome antibodies with disease flare in serologically active clinically quiescent patients with systemic lupus erythematosus. Arthritis Rheum 55:900–904

    Article  CAS  Google Scholar 

  31. Sui M, Sui M, Lin Q, Xu Z, Han X, Xie R et al (2013) Simultaneous positivity for anti-DNA, anti-nucleosome and anti-histone antibodies is a marker for more severe lupus nephritis. J Clin Immunol 33:378–387

    Article  CAS  Google Scholar 

  32. Stinton LM, Barr SG, Tibbles LA, Yilmaz S, Sar A, Benedikttson H et al (2007) Autoantibodies in lupus nephritis patients requiring renal transplantation. Lupus 16:394–400

    Article  CAS  Google Scholar 

  33. Sinico R, Radice A, Ikehata M, Giammarresi G, Corace C, Arrigo G et al (2005) Anti-C1q autoantibodies in lupus nephritis: Prevalence and clinical significance. Ann New York Acad of Sci 1050:193–200

    Article  CAS  Google Scholar 

  34. Siegert C, Daha M, Westedt ML, van der Voort E, Breedveld F (1991) IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus. J Rheumatol 18:230–234

    CAS  Google Scholar 

  35. Orbai A-M, Truedsson L, Sturfelt G, Nived O, Fang H, Alarcón GS et al (2015) Anti- C1q antibodies in systemic lupus erythematosus. Lupus 24:42–49

    Article  CAS  Google Scholar 

  36. Matrat A, Veysseyre-Balter C, Trolliet P, Villar E, Dijoud F, Bienvenu J et al (2011) Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: Predictive value for renal flares. Lupus 20:28–34

    Article  CAS  Google Scholar 

  37. Moroni G, Radice A, Giammarresi G, Quaglini S, Gallelli B, Leoni A et al (2009) Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis 68:234–237

    Article  CAS  Google Scholar 

  38. Choi M, FitzPatrick R, Buhler K, Mahler M, Fritzler M (2020) A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Autoimmun Rev 19:102463

  39. Haddouk S, Marzouk S, Jallouli M, Fourati H, Frigui M, Hmida Y et al (2009) Clinical and diagnostic value of ribosomal P autoantibodies in systemic lupus erythematosus. Rheumatology (Oxford) 48:953–957

    Article  CAS  Google Scholar 

  40. Bonfa E, Golombek S, Kaufman L, Skelly S, Weissbach H, Brot N et al (1987) Association between lupus psychosis and anti-ribosomal P protein antibodies. New Eng J Med 317:265–271

    Article  CAS  Google Scholar 

  41. do Nascimento A, Viana VDS, Testagossa LDA, Leon E, Borba E, Barros R et al (2006) Antibodies to ribosomal P proteins: a potential serologic marker for lupus membranous glomerulonephritis. Arthritis Rheum 54:1568–1572

  42. Macedo P, Borba E, Viana VDS, Leon E, Testagossa L, Barros R et al (2011) Antibodies to ribosomal P proteins in lupus nephritis: is a surrogate marker for a better renal survival? Autoimmun Rev 10:126–130

  43. Calich A, Viana V, Cancado E, Tustumi F, Terrabuio D, Leon E et al (2013) Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis. Liver Int 336:909–913

    Article  Google Scholar 

  44. Tektonidou M, Sotsiou F, Nakopoulou L, Vlachoyiannopoulos P, Moutsopoulos H (2004) Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies:Pprevalence, clinical associations, and long-term outcome. Arthritis Rheum 50:2569–2579

    Article  Google Scholar 

  45. Fayyaz A, Igoe A, Kurien BT, Danda D, James JA, Stafford HA et al (2015) Haematological manifestations of lupus. Lupus Sci Med 2:e000078

  46. Stegert M, Bock M, Trendelenburg M (2015) Clinical presentation of human C1q deficiency: How much of a lupus? Mol Immunol 67:3–11

    Article  CAS  Google Scholar 

  47. Araujo MNT, Silva NP, Andrade LEC, Sato EI, Gerbase-DeLima M, Leser PG (1997) C2 deficiency in blood donors and lupus patients: prevalence, clinical characteristics and HLA-associations in the Brazilian population. Lupus 6:462–466

    Article  CAS  Google Scholar 

  48. Yang Y, Chung EK, Wu YL, Savelli SL, Nagaraja HN, Zhou B et al (2007) Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): Low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet 80:1037–1054

    Article  CAS  Google Scholar 

  49. Pereira KMC, Perazzio S, Faria AGA, Moreira ES, Santos VC, Grecco M et al (2019) Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus. Adv Rheumatol 59:36–42

    Article  Google Scholar 

  50. Hughes G (1983) Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed) 287:1088–1089

    Article  CAS  Google Scholar 

  51. McNeil H, Simpson R, Chesterman C, Krilis S (1990) Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: Beta 2-glycoprotein I (apolipoprotein H). Proc Nati Acad Sci U S A 87:4120–4124

    Article  CAS  Google Scholar 

  52. Groot P, Urbanus R (2012) The significance of autoantibodies against β2-glycoprotein I. Blood 120:266–274

    Article  Google Scholar 

  53. Miyakis S, Lockshin M, Atsumi T, Branch D, Brey R, Cervera R et al (2006) International consensus statement on an update of the classification criteria for a definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306

    Article  CAS  Google Scholar 

  54. Barbhaiya M, Zuily S, Ahmadzadeh Y, Amigo MC, Avcin T, Bertolaccini ML et al (2020) Development of new international antiphospholipid syndrome classification criteria phase I/II Report: Generation and reduction of candidate criteria. Arthritis Care Res (Hoboken). Online ahead of print: https://doi.org/10.1002/acr.24520

  55. Urbanus R, Siegerink B, Roest M, Rosendaal F, de Groot P, Algra A (2009) Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 8:998–1005

    Article  CAS  Google Scholar 

  56. Devreese KMJ (2020) Testing for antiphospholipid antibodies: advances and best practices. Int J Lab Hematol 42(Suppl 1):49–58

    Article  Google Scholar 

  57. Jayakody Arachchillage D, Greaves M (2014) The checked history of the antiphospholipid syndrome. British J Haematol 165:609–617

    Article  Google Scholar 

  58. Reynaud Q, Lega J, Mismetti P, Chapelle C, Wahl D, Cathébras P et al (2014) Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev 13:595–608

    Article  CAS  Google Scholar 

  59. Schouwers SM, Delanghe JR, Devreese KM (2010) Lupus anticoagulant (LAC) testing in patients with inflammatory status: Does C-reactive protein interfere with LAC test results? Thromb Res 125:102–104

    Article  CAS  Google Scholar 

  60. Nayfe R, Uthman I, Aoun J, Saad Aldin E, Merashli M, Khamashta M (2013) Seronegative antiphospholipid syndrome. Rheumatology (Oxford) 52:1358–1367

    Article  Google Scholar 

  61. Murthy V, Willis R, Romay-Penabad Z, Ruiz-Limón P, Martínez-Martínez L, Jatwani S et al (2013) Value of isolated IgA anti-β2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome. Arthritis Rheum 65:3186–3193

    Article  CAS  Google Scholar 

  62. Morales J, Martinez-Flores J, Serrano M, Castro M, Alfaro F, García F et al (2015) Association of early kidney allograft failure with preformed IgA antibodies to β2-glycoprotein I. J Am Soc Nephrol (JASN) 26:735–745

    Article  CAS  Google Scholar 

  63. Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta M, Bertolaccini M (2014) Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost 111:354–364

    Article  CAS  Google Scholar 

  64. Litvinova E, Darnige L, Kirilovsky A, Burnel Y, Luna G, Dragon-Durey M (2018) Prevalence and significance of non-conventional antiphospholipid antibodies in patients with clinical APS criteria. Front Immunol 9:2971

    Article  CAS  Google Scholar 

  65. Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K et al (2012) Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum 64:504–512

    Article  CAS  Google Scholar 

  66. Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta M, Bertolaccini M (2013) GAPSS: The global anti-phospholipid syndrome score. Rheumatology (Oxford) 52:1397–1403

    Article  Google Scholar 

  67. Radin M, Cecchi I, Roccatello D, Meroni P, Sciascia S (2018) Prevalence and thrombotic risk assessment of anti-β2 Glycoprotein I domain I antibodies: a systematic review. Semin Thromb Hemost 44:466–474

    Article  CAS  Google Scholar 

  68. Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E et al (2015) Antiphospholipid syndrome: Antibodies to Domain 1 of β2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 13:782–787

    Article  CAS  Google Scholar 

  69. Nakamura H, Oku K, Amengual O, Ohmura K, Fujieda Y, Kato M et al (2018) First-line, non-criterial antiphospholipid antibody testing for the diagnosis of antiphospholipid syndrome in clinical practice: The combination of anti-β 2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin complex antibodies tests. Arthritis Care Res (Hoboken) 70:627–634

    Article  CAS  Google Scholar 

  70. Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Ninety F, Iliceto S (2005) Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 93:1147–1152

    Article  CAS  Google Scholar 

  71. Ruffatti A, Calligaro A, Hoxha A, Trevisanuto D, Ruffatti A, Gervasi M et al (2010) Laboratory and clinical features of pregnant women with antiphospholipid syndrome and neonatal outcome. Arthritis Care Res (Hoboken) 62:302–307

    Article  CAS  Google Scholar 

  72. Radin M, Sciascia S, Erkan D, Pengo V, Tektonidou M, Ugarte A et al (2019) The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort. Semin Arthritis Rheum 49:464–468

    Article  Google Scholar 

  73. Burgos-Vargas R, Catoggio LJ, Galarza-Maldonado C, Ostojich K, Cardiel MH (2013) Current therapies in rheumatoid arthritis: a Latin American perspective. Reumatol Clin 9:106–112

    Article  Google Scholar 

  74. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS et al (2018) Rheumatoid arthritis. Nat Rev Dis Primers 4:18001

    Article  Google Scholar 

  75. Greenblatt HK, Kim HA, Bettner LF, Deane KD (2020) Preclinical rheumatoid arthritis and rheumatoid arthritis prevention. Curr Opin Rheumatol 32:289–296

    Article  Google Scholar 

  76. Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A et al (2020) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 79:685–699

    Article  CAS  Google Scholar 

  77. Wu CY, Yang HY, Luo SF, Lai JH (2021) From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis. Int J Mol Sci 22:686

    Article  CAS  Google Scholar 

  78. Aletaha D (2020) Precision medicine and management of rheumatoid arthritis. J Autoimmun 110:102405

  79. Tarn JR, Lendrem DW, Isaacs JD (2020) In search of pathobiological endotypes: a systems approach to early rheumatoid arthritis. Expert Rev Clin Immunol 16:621–630

    Article  CAS  Google Scholar 

  80. Bettner LF, Peterson RA, Bergstedt DT, Kelmenson LB, Demoruelle MK, Mikuls TR et al (2021) Combinations of anticyclic citrullinated protein antibody, rheumatoid factor, and serum calprotectin positivity are associated with the diagnosis of rheumatoid arthritis within 3 years. ACR Open Rheumatol 20. https://doi.org/10.1002/acr2.11309

  81. Deane KD, Holers VM (2021) Rheumatoid arthritis pathogenesis, prediction, and prevention: an emerging paradigm shift. Arthritis Rheumatol 73:181–193

    Article  Google Scholar 

  82. Masi AT (1983) Articular patterns in the early course of rheumatoid arthritis. Am J Med 75:16–26

    Article  CAS  Google Scholar 

  83. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    Article  CAS  Google Scholar 

  84. Trouw LA, Huizinga TW, Toes RE (2013) Autoimmunity in rheumatoid arthritis: Different antigens—common principles. Ann Rheum Dis 72(Suppl 2):ii132–ii136

  85. Carubbi F, Alunno A, Gerli R, Giacomelli R (2019) Post-translational modifications of proteins: Novel insights in the autoimmune response in rheumatoid arthritis. Cells 8(7):657

  86. Grönwall C, Amara K, Hardt U, Krishnamurthy A, Steen J, Engstrom M et al (2017) Autoreactivity to malondialdehyde-modifications in rheumatoid arthritis is linked to disease activity and synovial pathogenesis. J Autoimmun 84:29–45

    Article  Google Scholar 

  87. Juarez M, Bang H, Hammar F, Reimer U, Dyke B, Sahbudin I et al (2016) Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis 75:1099–1107

    Article  CAS  Google Scholar 

  88. Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GM, van Veelen PA et al (2011) Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci USA 108:17372–17377

    Article  CAS  Google Scholar 

  89. de Brito RS, Baldo DC, Andrade LEC (2019) Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis. Adv Rheumatol 59:2

    Article  Google Scholar 

  90. Grönwall C, Liljefors L, Bang H, Hensvold AH, Hansson M, Mathsson-Alm L et al (2021) A comprehensive evaluation of the relationship between different IgG and IgA anti-modified protein autoantibodies in rheumatoid arthritis. Front Immunol 12:627986

  91. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  Google Scholar 

  92. Van Hoovels L, Jacobs J, Vander Cruyssen B, Van den Bremt S, Verschueren P, Bossuyt X (2018) Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis. Ann Rheum Dis 77:667–677

    Article  Google Scholar 

  93. Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S et al (2007) Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 146:797–808

    Article  Google Scholar 

  94. Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101:273–281

    Article  CAS  Google Scholar 

  95. Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163

    Article  CAS  Google Scholar 

  96. van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7:R949–R958

    Article  Google Scholar 

  97. Derksen VF, Ajeganova S, Trouw LA, van der Helm-van Mil AH, Hafström I, Huizinga TW et al (2017) Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present. Ann Rheum Dis 76:716–720

    Article  CAS  Google Scholar 

  98. Juarez M, Bang H, Hammar F, Reimer U, Dyke B, Sahbudin I et al (2016) Identification of novel anti-acetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis 75:1099–1107

    Article  CAS  Google Scholar 

  99. Combe B, Dougados M, Goupille P, Cantagrel A, Eliaou JF, Sibilia J et al (2001) Prognostic factors for radiographic damage in early rheumatoid arthritis: a multi parameter prospective study. Arthritis Rheum 44:1736–1743

    Article  CAS  Google Scholar 

  100. Bukhari M, Thomson W, Naseem H, Bunn D, Silman A, Symmons D et al (2007) The performance of anti-cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: Results from the Norfolk Arthritis Register. Arthritis Rheum 56:2929–2935

    Article  CAS  Google Scholar 

  101. Visser K, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ronday HK, Seys PE, Kerstens PJ et al (2010) A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: Post hoc analyses from the BeSt study. Ann Rheum Dis 69:1333–1337

    Article  CAS  Google Scholar 

  102. Jilani AA, Mackworth-Young CG (2015) The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: a systematic literature review and meta-analysis. Int J Rheumatol 2015:728610. https://doi.org/10.1155/2015/728610

    Article  CAS  Google Scholar 

  103. Klareskog L, Catrina AI, Paget S (2009) Rheumatoid arthritis. Lancet 373:659–672

    Article  CAS  Google Scholar 

  104. Jawaheer D, Thomson W, MacGregor AJ, Carthy D, Davidson J, Dyer PA et al (1994) Homozygosity for the HLA-DR shared epitope contributes the highest risk for rheumatoid arthritis concordance in identical twins. Arthritis Rheum 37:681–686

    Article  CAS  Google Scholar 

  105. Alarcon RT, Fernandes AR, Laurindo IM, Bértolo MB, Pinheiro GC, Andrade LE (2015) Characterization of cumulative joint damage patterns in patients with rheumatoid arthritis: a clinical, serological, and gene polymorphism perspective. J Rheumatol 42:405–412

    Article  Google Scholar 

  106. Viatte S, Lee JC, Fu B, Espéli M, Lunt M, De Wolf JN et al (2016) Association between genetic variation in FOXO3 and reductions in inflammation and disease activity in inflammatory polyarthritis. Arthritis Rheumatol 68:2629–2636

    Article  CAS  Google Scholar 

  107. Krabben A, Huizinga TW, Mil AH (2015) Biomarkers for radiographic progression in rheumatoid arthritis. Curr Pharm Des 21:147–169

    Article  CAS  Google Scholar 

  108. Lee JC, Espéli M, Anderson CA, Linterman MA, Pocock JM, Williams NJ et al (2013) Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell 155:57–69

    Article  CAS  Google Scholar 

  109. van Nies JA, Tsonaka R, Gaujoux-Viala C, Fautrel B, van der Helm-van Mil AH (2015) Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: Does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts. Ann Rheum Dis 74:806–812

    Article  Google Scholar 

  110. Aho K, Palosuo T, Raunio V, Puska P, Aromaa A, Salonen JT (1985) When does rheumatoid disease start? Arthritis Rheum 28:485–489

    Article  CAS  Google Scholar 

  111. Rantapää-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48:2741–2749

    Article  Google Scholar 

  112. Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH et al (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50:380–386

    Article  Google Scholar 

  113. Rakieh C, Nam JL, Hunt L, Hensor EM, Das S, Bissell LA et al (2015) Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis 74:1659–1666

    Article  CAS  Google Scholar 

  114. Bos WH, Wolbink GJ, Boers M, Tijhuis GJ, de Vries N, van der Horst-Bruinsma IE et al (2010) Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann Rheum Dis 69:490–494

    Article  CAS  Google Scholar 

  115. Verheul MK, Böhringer S, van Delft MAM, Jones JD, Rigby WFC, Gan RW et al (2018) Triple positivity for anti-citrullinated protein autoantibodies, rheumatoid factor, and anti-carbamylated protein antibodies conferring high specificity for rheumatoid arthritis: Implications for very early identification of at-risk individuals. Arthritis Rheumatol 70:1721–1731

    Article  CAS  Google Scholar 

  116. Viatte S, Plant D, Bowes J, Lunt M, Eyre S, Barton A et al (2012) Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients. Ann Rheum Dis 71:1984–1990

    Article  CAS  Google Scholar 

  117. Viatte S, Massey J, Bowes J, Duffus K, arcOGEN Consortium, Eyre S et al (2016) Replication of associations of genetic loci outside the HLA region with susceptibility to anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheumatol 68:1603–1613

  118. Källberg H, Ding B, Padyukov L, Bengtsson C, Rönnelid J, Klareskog L et al (2011) Smoking is a major preventable risk factor for rheumatoid arthritis: Estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis 70:508–511

    Article  Google Scholar 

  119. Bettner LF, Peterson RA, Bergstedt DT, Kelmenson LB, Demoruelle MK, Mikuls TR et al (2021) Combinations of anti-cyclic citrullinated protein antibody, rheumatoid factor, and serum calprotectin positivity are associated with the diagnosis of rheumatoid arthritis within 3 years. ACR Open Rheumatol. https://doi.org/10.1002/acr2.11309

    Article  Google Scholar 

  120. Jarlborg M, Courvoisier DS, Lamacchia C, Martinez-Prat L, Mahler M, Bentow C et al (2020) Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthritis. Arthritis Res Ther 22:105

    Article  CAS  Google Scholar 

  121. de Moel EC, Rech J, Mahler M, Roth J, Vogl T, Schouffoer A et al (2019) Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs. Arthritis Res Ther 21:268

    Article  Google Scholar 

  122. Courvoisier DS, Chatzidionysiou K, Mongin D, Lauper K, Mariette X, Morel J et al (2021) The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: Results from a collaboration of 16 registries. Rheumatology (Oxford) 60:820–828

    Article  CAS  Google Scholar 

  123. Bird P, Hall S, Nash P, Connell CA, Kwok K, Witcombe D et al (2019) Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in phase III randomised clinical trials of tofacitinib. RMD Open 5:e000742

  124. Schlager L, Loiskandl M, Aletaha D, Radner H (2020) Predictors of successful discontinuation of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review. Rheumatology (Oxford) 59:324–334

    Article  Google Scholar 

  125. Fox RI (2005) Sjögren’s syndrome. Lancet 366:321–331

    Article  CAS  Google Scholar 

  126. Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F et al (2015) Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis. Ann Rheum Dis 74:1983–1989

    Article  CAS  Google Scholar 

  127. Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM (1999) Malignant lymphoma in primary Sjögren’s syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjögren’s Syndrome. Arthritis Rheum 42:1765–1772

    Article  CAS  Google Scholar 

  128. Kroese FG, Abdulahad WH, Haacke E, Bos NA, Vissink A, Bootsma H (2014) B-cell hyperactivity in primary Sjögren’s syndrome. Expert Rev Clin Immunol 10:483–499

    Article  CAS  Google Scholar 

  129. Ramos-Casals M, Tzioufas AG, Font J (2005) Primary Sjögren’s syndrome: New clinical and therapeutic concepts. Ann Rheum Dis 64:347–354

    Article  CAS  Google Scholar 

  130. Brito-Zerón P, Acar-Denizli N, Ng WF, Zeher M, Rasmussen A, Mandl T et al (2018) How immunological profile drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: Analysis of 10,500 patients (Sjögren Big Data Project). Clin Exp Rheumatol 36(Suppl 112(3)):102–112

  131. Goules AV, Exarchos TP, Pezoulas VC, Kourou KD, Venetsanopoulou AI, De Vita S et al (2019) Sjögren’s syndrome towards precision medicine: the challenge of harmonisation and integration of cohorts. Clin Exp Rheumatol 37(Suppl 118):175–184

    Google Scholar 

  132. Theander E, Jonsson R, Sjöström B, Brokstad K, Olsson P, Henriksson G (2015) Prediction of Sjögren’s syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling. Arthritis Rheumatol 67:2427–2436

    Article  CAS  Google Scholar 

  133. Andrade LE, Chan EK, Peebles CL, Tan EM (1996) Two major autoantigen-antibody systems of the mitotic spindle apparatus. Arthritis Rheum 39:1643–1653

    Article  CAS  Google Scholar 

  134. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM et al (2017) 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 76:9–16

    Article  Google Scholar 

  135. Alspaugh MA, Talal N, Tan EM (1976) Differentiation and characterization of autoantibodies and their antigens in Sjögren’s syndrome. Arthritis Rheum 19:216–222

    Article  CAS  Google Scholar 

  136. Wolin SL, Reinisch KM (2006) The Ro 60 kDa autoantigen comes into focus: Interpreting epitope mapping experiments on the basis of structure. Autoimmun Rev 5:367–372

    Article  CAS  Google Scholar 

  137. Oke V, Wahren-Herlenius M (2012) The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review. J Autoimmun 39:77–82

    Article  CAS  Google Scholar 

  138. Mekinian A, Nicaise-Roland P, Chollet-Martin S, Fain O, Crestani B (2013) Anti-SSA Ro52/Ro60 antibody testing by immunodot could help the diagnosis of Sjogren’s syndrome in the absence of anti-SSA/SSB antibodies by ELISA. Rheumatology (Oxford) 52:2223–2228

    Article  CAS  Google Scholar 

  139. Robbins A, Hentzien M, Toquet S, Didier K, Servettaz A, Pham BN et al (2019) Diagnostic utility of separate anti-Ro60 and anti-Ro52/TRIM21 antibody detection in autoimmune diseases. Front Immunol 10:444. https://doi.org/10.3389/fimmu.2019.00444

    Article  CAS  Google Scholar 

  140. Ghillani P, André C, Toly C, Rouquette AM, Bengoufa D, Nicaise P et al (2011) Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: Results of a multicentric study. Autoimmun Rev 10:509–513

    Article  CAS  Google Scholar 

  141. Retamozo S, Akasbi M, Brito-Zerón P, Bosch X, Bove A, Perez-de-Lis M et al (2012) Anti-Ro52 antibody testing influences the classification and clinical characterisation of primary Sjögren’s syndrome. Clin Exp Rheumatol 30:686–692

    Google Scholar 

  142. Buvry C, Cassagnes L, Tekath M, Artigues M, Pereira B, Rieu V et al (2020) Anti-Ro52 antibodies are a risk factor for interstitial lung disease in primary Sjögren syndrome. Respir Med 163:105895. https://doi.org/10.1016/j.rmed.2020.105895

    Article  Google Scholar 

  143. Quartuccio L, Baldini C, Bartoloni E, Priori R, Carubbi F, Corazza L et al (2015) Anti-SSA/SSB-negative Sjögren’s syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution. Autoimmun Rev 14:1019–1022

    Article  CAS  Google Scholar 

  144. ter Borg EJ, Kelder JC (2014) Lower prevalence of extra-glandular manifestations and anti-SSB antibodies in patients with primary Sjögren’s syndrome and widespread pain: Evidence for a relatively benign subset. Clin Exp Rheumatol 32:349–353

    Google Scholar 

  145. Baer AN, McAdams DeMarco M, Shiboski SC, Lam MY, Challacombe S, Daniels TE et al (2015) The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren’s syndrome. Ann Rheum Dis 74:1557–1561

    Article  CAS  Google Scholar 

  146. Acar-Denizli N, Horváth IF, Mandl T, Priori R, Vissink A, Hernandez-Molina G et al (2020) Systemic phenotype related to primary Sjögren’s syndrome in 279 patients carrying isolated anti-La/SSB antibodies. Clin Exp Rheumatol 38(Suppl 126):85–94

    Google Scholar 

  147. Baer AN, Medrano L, McAdams-DeMarco M, Gniadek TJ (2016) Association of anticentromere antibodies with more severe exocrine glandular dysfunction in Sjögren’s syndrome: Analysis of the Sjögren’s International Collaborative Clinical Alliance Cohort. Arthritis Care Res (Hoboken) 68:1554–1559

    Article  CAS  Google Scholar 

  148. Ryu YS, Park SH, Lee J, Kwok SK, Ju JH, Kim HY et al (2013) Follow-up of primary Sjogren’s syndrome patients presenting positive anti-cyclic citrullinated peptides antibody. Rheumatol Int 33:1443–1446

    Article  Google Scholar 

  149. Ramos-Casals M, Stone JH, Cid MC, Bosch X (2012) The cryoglobulinaemias. Lancet 379:348–360

    Article  CAS  Google Scholar 

  150. La Civita L, Zignego AL, Monti M, Longombardo G, Pasero G, Ferri C (1995) Mixed cryoglobulinemia as a possible preneoplastic disorder. Arthritis Rheum 38:1859–1860

    Article  Google Scholar 

  151. Brito-Zerón P, Kostov B, Solans R, Fraile G, Suárez-Cuervo C, Casanovas A et al (2016) Systemic activity and mortality in primary Sjögren syndrome: Predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. Ann Rheum Dis 75:348–355

    Article  Google Scholar 

  152. Quartuccio L, Isola M, Baldini C, Priori R, Bocci EB, Carubbi F et al (2014) Biomarkers of lymphoma in Sjögren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. J Autoimmun 51:75–80

    Article  Google Scholar 

  153. Legatowicz-Koprowska M, Nitek S, Czerwińska J (2020) The complement system in primary Sjögren’s syndrome: The expression of certain cascade and regulatory proteins in labial salivary glands – observational study. Reumatologia 58:357–366

    Article  Google Scholar 

  154. Baimpa E, Dahabreh IJ, Voulgarelis M, Moutsopoulos HM (2009) Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: Clinical and pathophysiologic aspects. Medicine (Baltimore) 88:284–293

    Article  Google Scholar 

  155. Brito-Zerón P, Retamozo S, Gandía M, Akasbi M, Pérez-De-Lis M, Diaz-Lagares C et al (2012) Monoclonal gammopathy related to Sjögren syndrome: a key marker of disease prognosis and outcomes. J Autoimmun 39:43–48

    Article  Google Scholar 

  156. Denton CP, Khanna D (2017) Systemic sclerosis. Lancet 390:1685–1699

    Article  Google Scholar 

  157. Chifflot H, Fautrel B, Sordet C, Chatelus E, Sibilia J (2008) Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum 37:223–235

    Article  Google Scholar 

  158. Medsger TA Jr (2003) Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum Dis Clin North Am 29:255–273

    Article  Google Scholar 

  159. Steen VD (2005) Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 35:35–42

    Article  CAS  Google Scholar 

  160. Kayser C, Fritzler MJ (2015) Autoantibodies in systemic sclerosis: Unanswered questions. Front Immunol 6:167

    Article  Google Scholar 

  161. Mehra S, Walker J, Patterson K, Fritzler MJ (2013) Autoantibodies in systemic sclerosis. Autoimmun Rev 12:340–354

    Article  CAS  Google Scholar 

  162. Sirotti S, Generali E, Ceribelli A, Isailovic N, De Santis M, Selmi C (2017) Personalized medicine in rheumatology: The paradigm of serum autoantibodies. Autoimmun Highlights 8:10

    Article  Google Scholar 

  163. Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 66:754–763

    Article  CAS  Google Scholar 

  164. Hu PQ, Fertig N, Medsger TA Jr, Wright TM (2003) Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis Rheum 48:1363–1373

    Article  CAS  Google Scholar 

  165. Kuwana M, Kaburaki J, Okano Y, Tojo T, Homma M (1994) Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum 37:75–83

    Article  CAS  Google Scholar 

  166. Shah AA, Hummers LK, Casciola-Rosen L, Visvanathan K, Rosen A, Wigley FM (2015) Examination of autoantibody status and clinical features associated with cancer risk and cancer associated scleroderma. Arthritis Rheumatol 67:1053–1061

    Article  CAS  Google Scholar 

  167. Roofeh D, Khanna D (2020) Management of systemic sclerosis: The first five years. Curr Opin Rheumatol 32:228–237

    Article  Google Scholar 

  168. Saito A, Muro Y, Sugiura K, Akiyama M (2013) Low prevalence of autoantibodies to CENP-H, -I, -K, -L, -M, -N, -T and -U in a Japanese cohort of anti-centromere positive samples. Immunopharmacol Immunotoxicol 35:57–63

    Article  CAS  Google Scholar 

  169. Patterson KA, Roberts-Thomson PJ, Lester S, Tan JA, Hakendorf P, Rischmueller M et al (2015) Interpretation of an extended autoantibody profile in a well-characterized Australian systemic sclerosis (scleroderma) cohort using principal components analysis. Arthritis Rheumatol 67:3234–3244

    Article  CAS  Google Scholar 

  170. Kallenberg CG, Wouda AA, Hoet MH, van Venrooij WJ (1988) Development of connective tissue disease in patients presenting with Raynaud’s phenomenon: a six-year follow-up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis 47:634–641

    Article  CAS  Google Scholar 

  171. Salliot C, Gottenberg JE, Bengoufa D, Desmoulins F, Miceli-Richard C, Mariette X (2007) Anti-centromere antibodies identify patients with Sjögren’s syndrome and autoimmune overlap syndrome. J Rheumatol 34:2253–2258

    CAS  Google Scholar 

  172. Hamaguchi Y, Kodera M, Matsushita T, Hasegawa M, Inaba Y, Usuda T et al (2015) Clinical and immunologic predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies. Arthritis Rheumatol 67:1045–1052

    Article  CAS  Google Scholar 

  173. Lazzaroni MG, Cavazzana I, Colombo E, Dobrota R, Hernandez J, Hesselstrand R et al (2017) Malignancies in patients with anti-RNA polymerase III antibodies and systemic sclerosis: Analysis of the EULAR scleroderma trials and research cohort and possible recommendations for screening. J Rheumatol 44:639–647

    Article  CAS  Google Scholar 

  174. Phan TG, Cass A, Gillin A, Trew P, Fertig N, Sturgess A (1999) Anti-RNA polymerase III antibodies in the diagnosis of scleroderma renal crisis sine scleroderma. J Rheumatol 26:2489–2492

    CAS  Google Scholar 

  175. Ceribelli A, Cavazzana I, Airo P, Franceschini F (2010) Anti-RNA polymerase III antibodies as a risk marker for early gastric antral vascular ectasia (GAVE) in systemic sclerosis. J Rheumatol 37:1544

    Article  Google Scholar 

  176. Sharif R, Fritzler MJ, Mayes MD, Gonzalez EB, McNearney TA, Draeger H et al (2011) Anti-fibrillarin antibody in African American patients with systemic sclerosis: Immunogenetics, clinical features, and survival analysis. J Rheumatol 38:1622–1630

    Article  CAS  Google Scholar 

  177. Aggarwal R, Lucas M, Fertig N, Oddis CV, Medsger TA Jr (2009) Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum 60:1112–1118

    Article  Google Scholar 

  178. Mitri GM, Lucas M, Fertig N, Steen VD, Medsger TA Jr (2003) A comparison between anti-Th/To- and anticentromere antibody-positive systemic sclerosis patients with limited cutaneous involvement. Arthritis Rheum 48:203–209

    Article  Google Scholar 

  179. Fischer A, Pfalzgraf FJ, Feghali-Bostwick CA, Wright TM, Curran-Everett D, West SG et al (2006) Anti-Th/To-positivity in a cohort of patients with idiopathic pulmonary fibrosis. J Rheumatol 33:1600–1605

    Google Scholar 

  180. Hudson M, Pope J, Mahler M, Tatibouet S, Steele R, Baron M et al (2012) Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis. Arthritis Res Ther 14:R50

    Article  CAS  Google Scholar 

  181. Fertig N, Domsic RT, Rodriguez-Reyna T, Kuwana M, Lucas M, Medsger TA Jr et al (2009) Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis Rheum 61:958–965

    Article  CAS  Google Scholar 

  182. Mierau R, Moinzadeh P, Riemekasten G, Melchers I, Meurer M, Reichenberger F et al (2011) Frequency of disease-associated and other nuclear autoantibodies in patients of the German Network for Systemic Scleroderma: Correlation with characteristic clinical features. Arthritis Res Ther 13:R172

    Article  CAS  Google Scholar 

  183. Muro Y, Hosono Y, Sugiura K, Ogawa Y, Mimori T, Akiyama M (2015) Anti-PM/Scl antibodies are found in Japanese patients with various systemic autoimmune conditions besides myositis and scleroderma. Arthritis Res Ther 17:57

    Article  Google Scholar 

  184. Hoa S, Hudson M, Troyanov Y, Proudman S, Walker J, Stevens W et al (2016) Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: Clinical associations. Medicine (Baltimore) 95:e4713

  185. Fujii T, Mimori T, Akizuki M (1996) Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patients with rheumatic diseases, by recombinant autoantigen-based assays. Arthritis Rheum 39:1313–1318

    Article  CAS  Google Scholar 

  186. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347

    Article  CAS  Google Scholar 

  187. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292:403–407

    Article  CAS  Google Scholar 

  188. Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F et al (2018) Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol 75:1528–1537

    Article  Google Scholar 

  189. Tanboon J, Uruha A, Stenzel W, Nishino I (2020) Where are we moving in the classification of idiopathic inflammatory myopathies? Curr Opin Neurol 33:590–603

    Article  CAS  Google Scholar 

  190. Meyer A, Meyer N, Schaeffer M, Gottenberg JE, Geny B, Sibilia J (2015) Incidence and prevalence of inflammatory myopathies: a systematic review. Rheumatology (Oxford) 54:50–63

    Article  CAS  Google Scholar 

  191. Riddell V, Bagby S, McHugh N (2020) Myositis autoantibodies: recent perspectives. Curr Opin Rheumatol 32:548–552

    Article  CAS  Google Scholar 

  192. Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EKL (2017) Comprehensive overview on myositis-specific antibodies: New and old biomarkers in idiopathic inflammatory myopathy. Clin Rev Allergy Immunol 52:1–19

    Article  CAS  Google Scholar 

  193. Mahler M, Miller FW, Fritzler MJ (2014) Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 13:367–371

    Article  CAS  Google Scholar 

  194. Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A et al (2001) Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 60:116–123

    Article  CAS  Google Scholar 

  195. Aggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP et al (2014) Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 73:227–232

    Article  Google Scholar 

  196. Mammen AL (2011) Autoimmune myopathies: Autoantibodies, phenotypes and pathogenesis. Nat Rev Neurol 7:343–354

    Article  CAS  Google Scholar 

  197. Okiyama N (2021) Clinical features and cutaneous manifestations of juvenile and adult patients of dermatomyositis associated with myositis-specific autoantibodies. J Clin Med 10:1725

    Article  CAS  Google Scholar 

  198. Fujimoto M, Hamaguchi Y, Kaji K, Matsushita T, Ichimura Y, Kodera M et al (2012) Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 64:513–522

    Article  CAS  Google Scholar 

  199. Palterer B, Vitiello G, Carraresi A, Giudizi MG, Cammelli D, Parronchi P (2018) Bench to bedside review of myositis autoantibodies. Clin Mol Allergy 16:5–22

    Article  Google Scholar 

  200. Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N et al (2012) The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford) 51:1278–1284

    Article  CAS  Google Scholar 

  201. Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L (2011) The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol 65:25–34

    Article  Google Scholar 

  202. Betteridge Z, Gunawardena H, North J, Slinn J, McHugh N (2007) Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis. Arthritis Rheum 56:3132–3137

    Article  CAS  Google Scholar 

  203. Basharat P, Christopher-Stine L (2015) Immune-mediated necrotizing myopathy: Update on diagnosis and management. Curr Rheumatol Rep 17:72

    Article  Google Scholar 

  204. Pluk H, van Hoeve BJ, van Dooren SH, Stammen-Vogelzangs J, van der Heijden A, Schelhaas HJ et al (2013) Autoantibodies to cytosolic 5’-nucleotidase 1A in inclusion body myositis. Ann Neurol 73:397–407

    Article  CAS  Google Scholar 

  205. Amlani A, Choi MY, Tarnopolsky M, Brady L, Clarke AE, Garcia-De La Torre I et al (2019) Anti-NT5c1A autoantibodies as biomarkers in inclusion body myositis. Front Immunol 10:745

  206. Herbert MK, Stammen-Vogelzangs J, Verbeek MM, Rietveld A, Lundberg IE, Chinoy H et al (2016) Disease specificity of autoantibodies to cytosolic 5’-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis 75:696–701

    Article  CAS  Google Scholar 

  207. Rietveld A, Wienke J, Visser E, Vree Egberts W, Schlumberger W, van Engelen B et al (2021) Juvenile Dermatomyositis Research Group and the Dutch Myositis Consortium. Anti-Cytosolic 5'-nucleotidase 1A autoantibodies are absent in juvenile dermatomyositis. Arthritis Rheumatol 73:1329–1333

  208. European Association for the Study of the Liver (2015) EASL clinical practice guidelines: Autoimmune hepatitis. J Hepatol 63:971–1004

    Article  Google Scholar 

  209. European Association for the Study of the Liver (2017) EASL clinical practice guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67:145–172

    Article  Google Scholar 

  210. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ et al (2009) Primary biliary cirrhosis. Hepatology 50:291–308

    Article  Google Scholar 

  211. Manns MP, Lohse AW, Vergani D (2015) Autoimmune hepatitis – update 2015. J Hepatol 62:100–111

    Article  Google Scholar 

  212. Sebode M, Weiler-Normann C, Liwinski T, Schramm C (2018) Autoantibodies in autoimmune liver disease-clinical and diagnostic relevance. Front Immunol 9:609

    Article  Google Scholar 

  213. Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M et al (1997) Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 25:541–547

    Article  CAS  Google Scholar 

  214. Homberg JC, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil SH et al (1987) Chronic active hepatitis associated with anti-liver/kidney microsome antibody type 1: a second type of autoimmune hepatitis. Hepatology 7:1333–1339

    Article  CAS  Google Scholar 

  215. Martini E, Abuaf N, Cavalli F, Durand V, Johanet C, Homberg JC (1988) Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology 8:1662–1666

    Article  CAS  Google Scholar 

  216. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S (2004) Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 38:801–804

    Article  Google Scholar 

  217. Vergani D, Alvarez F, Bianchi FB, Cançado EL, Mackay IR, Manns MP et al (2004) Liver autoimmune serology: a consensus statement from the Committee for Autoimmune Serology of the International Autoimmune Hepatitis Group. J Hepatol 41:677–683

    Article  Google Scholar 

  218. Frenzel C, Herkel J, Lüth S, Galle PR, Schramm C, Lohse AW (2006) Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis. Am J Gastroenterol 101:2731–2736

    Article  CAS  Google Scholar 

  219. Liaskos C, Bogdanos DP, Davies ET, Dalekos GN (2007) Diagnostic relevance of anti-filamentous actin antibodies in autoimmune hepatitis. J Clin Pathol 60:107–108

    Article  CAS  Google Scholar 

  220. Terjung B, Worman HJ, Herzog V, Sauerbruch T, Spengler U (2001) Differentiation of antineutrophil nuclear antibodies in inflammatory bowel and autoimmune liver diseases from antineutrophil cytoplasmic antibodies (p-ANCA) using immunofluorescence microscopy. Clin Exp Immunol 126:37–46

    Article  CAS  Google Scholar 

  221. Gueguen M, Meunier-Rotival M, Bernard O, Alvarez F (1988) Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily. J Exp Med 168:801–806

    Article  CAS  Google Scholar 

  222. Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF (1989) Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J Clin Invest 83:1066–1072

    Article  CAS  Google Scholar 

  223. Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA (1988) Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proc Natl Acad Sci USA 85:8256–8260

    Article  CAS  Google Scholar 

  224. Lapierre P, Hajoui O, Homberg JC, Alvarez F (1999) Formiminotransferase cyclo-deaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis. Gastroenterology 116:643–649

    Article  CAS  Google Scholar 

  225. Lenzi M, Manotti P, Muratori L, Cataleta M, Ballardini G, Cassani F et al (1995) Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. Gut 36:749–754

    Article  CAS  Google Scholar 

  226. Kanzler S, Weidemann C, Gerken G, Löhr HF, Galle PR, zum Büschenfelde KHM et al (1999) Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis. J Hepatol 31:635–640

  227. Kirstein MM, Metzler F, Geiger E, Heinrich E, Hallensleben M, Manns MP et al (2015) Prediction of short- and long-term outcome in patients with autoimmune hepatitis. Hepatology 62:1524–1535

    Article  CAS  Google Scholar 

  228. Montano-Loza AJ, Shums Z, Norman GL, Czaja AJ (2012) Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis. Liver Int 32:85–92

    Article  CAS  Google Scholar 

  229. Rigopoulou EI, Roggenbuck D, Smyk DS, Liaskos C, Mytilinaiou MG, Feist E et al (2012) Asialoglycoprotein receptor (ASGPR) as target autoantigen in liver autoimmunity: Lost and found. Autoimmun Rev 12:260–269

    Article  CAS  Google Scholar 

  230. Liberal R, Mieli-Vergani G, Vergani D (2013) Clinical significance of autoantibodies in autoimmune hepatitis. J Autoimmun 46:17–24

    Article  CAS  Google Scholar 

  231. Selmi C, Ceribelli A, Generali E, Scirè CA, Alborghetti F, Colloredo G et al (2016) Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years. Autoimmun Rev 15:162–166

    Article  Google Scholar 

  232. Satoh M, Chan EK, Ho LA, Rose KM, Parks CG, Cohn RD et al (2012) Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum 64:2319–2327

    Article  Google Scholar 

  233. Agustinelli RA, Rodrigues SH, Mariz HA, Prado MS, Andrade LEC (2019) Distinctive features of positive anti-cell antibody tests (indirect immunofluorescence on HEp-2 cells) in patients with non-autoimmune diseases. Lupus 28:629–634

    Article  CAS  Google Scholar 

  234. Keppeke GD, Nunes E, Ferraz ML, Silva EA, Granato C, Chan EK et al (2012) Longitudinal study of a human drug-induced model of autoantibody to cytoplasmic rods/rings following HCV therapy with ribavirin and interferon-α. PLoS One 7:e45392

  235. Carcamo WC, Ceribelli A, Calise SJ, Krueger C, Chen L, Daves M et al (2013) Differential reactivity to IMPDH2 by anti-rods/rings autoantibodies and unresponsiveness to pegylated interferon-alpha/ribavirin therapy in US and Italian HCV patients. J Clin Immunol 33:420–426

    Article  CAS  Google Scholar 

  236. Calise SJ, Chan EKL (2020) Anti-rods/rings autoantibody and IMPDH filaments: an update after fifteen years of discovery. Autoimmun Rev19:102643

  237. Desmet VJ, Gerber M, Hoofnaagle JH, Manns M, Scheuer PJ (1994) Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 19:1513–1520

    Article  CAS  Google Scholar 

  238. Manns M, Gerken G, Kyriatsoulis A, Staritz M, zum Buschenfelde KHM (1987) Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1:292–294

  239. Baeres M, Herkel J, Czaja AJ, Wies I, Kanzler S, Cancado EL et al (2002) Establishment of standardised SLA/LP immunoassays: Specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut 51:259–264

    Article  CAS  Google Scholar 

  240. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB (1993) Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology 105:1502–1507

    Article  CAS  Google Scholar 

  241. O’Brien C, Joshi S, Feld JJ, Guindi M, Dienes HP, Heathcote EJ (2008) Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology 48:550–556

    Article  Google Scholar 

  242. Dinani AM, Fischer SE, Mosko J, Guindi M, Hirschfield GM (2012) Patients with autoimmune hepatitis who have antimitochondrial antibodies need longterm follow-up to detect late development of primary biliary cirrhosis. Clin Gastroenterol Hepatol 10:682–684

    Article  Google Scholar 

  243. Leung PS, Rossaro L, Davis PA, Park O, Tanaka A, Kikuchi K et al (2007) Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis. Hepatology 46:1436–1442

    Article  CAS  Google Scholar 

  244. Rigopoulou EI, Davies ET, Bogdanos DP, Liaskos C, Mytilinaiou M, Koukoulis GK et al (2007) Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis. Liver Int 27:1226–1231

    Article  CAS  Google Scholar 

  245. Corpechot C, Chazouilleres O, Poupon R (2011) Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 55:1361–1367

    Article  CAS  Google Scholar 

  246. Muratori P, Muratori L, Cassani F, Terlizzi P, Lenzi M, Rodrigo L et al (2002) Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders. Clin Exp Immunol 127:172–175

    Article  CAS  Google Scholar 

  247. Andre C, Guillemin MC, Zhu J, Koken MH, Quignon F, Herve L et al (1996) The PML and PML/RARalpha domains: From autoimmunity to molecular oncology and from retinoic acid to arsenic. Exp Cell Res 229:253–260

    Article  CAS  Google Scholar 

  248. Zuchner D, Sternsdorf T, Szostecki C, Heathcote EJ, Cauch-Dudek K, Will H (1997) Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatology 26:1123–1130

    CAS  Google Scholar 

  249. Czaja AJ (2010) Autoantibodies as prognostic markers in autoimmune liver disease. Dig Dis Sci 55:2144–2161

    Article  CAS  Google Scholar 

  250. Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M et al (2007) Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology 45:118–127

    Article  CAS  Google Scholar 

  251. Sfakianaki O, Koulentaki M, Tzardi M, Tsangaridou E, Theodoropoulos PA, Castanas E et al (2010) Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients. World J Gastroenterol 16:4938–4943

    Article  Google Scholar 

  252. Liberal R, Grant CR, Sakkas L, Bizzaro N, Bogdanos DP (2013) Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis. Clin Res Hepatol Gastroenterol 37:572–585

    Article  CAS  Google Scholar 

  253. Norman GL, Reig A, Viñas O, Mahler M, Wunsch E, Milkiewicz P et al (2019) The prevalence of anti-hexokinase-1 and anti-Kelch-like 12 peptide antibodies in patients with primary biliary cholangitis is similar in Europe and North America: a large international, multi-center study. Front Immunol 10:662

    Article  CAS  Google Scholar 

  254. Chazouillères O (2015) Overlap syndromes. Dig Dis Basel Switz 33(Suppl 2):181–187

    Article  Google Scholar 

  255. Silveira MG, Talwalkar JA, Angulo P, Lindor KD (2007) Overlap of autoimmune hepatitis and primary biliary cirrhosis: Long-term outcomes. Am J Gastroenterol 102:1244–1250

    Article  Google Scholar 

  256. Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R (1998) Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatol Baltim Md 28:296–301

    Article  Google Scholar 

  257. Nguyen HH, Shaheen AA, Baeza N, Lytvyak F, Urbanski SJ, Mason AL et al (2018) Evaluation of classical and novel autoantibodies for the diagnosis of primary biliary cholangitis–autoimmune hepatitis overlap syndrome (PBC-AIH OS). PLoS One 13:e0193960

  258. Muratori P, Granito A, Pappas G, Pendino GM, Quarneti C, Cicola R et al (2009) The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol 104:1420–1425

    Article  Google Scholar 

  259. Himoto T, Yoneyama H, Kurokohchi K, Inukai M, Masugata H, Goda F et al (2012) Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases. Can J Gastroenterol 26:125–129

    Article  Google Scholar 

  260. Höftberger R (2015) Neuroimmunology: an expanding frontier in autoimmunity. Front Immunol 6:1–5

    Article  Google Scholar 

  261. Flanagan EP (2019) Neuromyelitis optica spectrum disorder and other non-multiple sclerosis central nervous system inflammatory diseases. Continuum (Minneap Minn) 25:815–844

    Google Scholar 

  262. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

    Article  CAS  Google Scholar 

  263. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189

    Article  Google Scholar 

  264. Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J et al (2019) Eculizumab in aquaporin-4–positive neuromyelitis optica spectrum disorder. N Engl J Med 381:614–625

    Article  CAS  Google Scholar 

  265. Reindl M, Jarius S, Rostasy K, Berger T (2017) Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they? Curr Opin Neurol 30:295–301

    Article  CAS  Google Scholar 

  266. Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J et al (2018) MOG encephalomyelitis: International recommendations on diagnosis and antibody testing. Nervenarzt 89:1388–1399

    Article  CAS  Google Scholar 

  267. dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K et al (2018) MOG-IgG-associated optic neuritis, encephalitis, and myelitis: Lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 9:1–10

    Google Scholar 

  268. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, De Haidar Jorge FM, Takahashi T et al (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82:474–481

    Article  CAS  Google Scholar 

  269. Hennes EM, Baumann M, Schanda K, Anlar B, Bajer-Kornek B, Blaschek A et al (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908

    Article  CAS  Google Scholar 

  270. López-Chiriboga AS, Majed M, Fryer J, Dubey D, McKeon A, Flanagan EP et al (2018) Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG–associated disorders. JAMA Neurol 75:1355–1363

    Article  Google Scholar 

  271. Graus F, Saiz A, Dalmau J (2020) GAD antibodies in neurological disorders — insights and challenges. Nat Rev Neurol 16:353–365

  272. Ariño H, Höftberger R, Gresa-Arribas N, Martínez-Hernández E, Armangue T, Kruer MC et al (2015) Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 72:1–8

    Article  Google Scholar 

  273. Muñoz-Lopetegi A, de Bruijn MAAM, Boukhrissi S, Bastiaansen AEM, Nagtzaam MMP, Hulsenboom ESP et al (2020) Neurologic syndromes related to anti-GAD65. Neurol Neuroimmunol Neuroinflammation 7:e696

  274. Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378:840–851

    Article  Google Scholar 

  275. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404

    Article  Google Scholar 

  276. Van Coevorden-Hameete MH, de Graaff E, Titulaer MJ, Hoogenraad CC, Sillevis Smitt PAE (2014) Molecular and cellular mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system. Autoimmun Rev 13:299–312

    Article  Google Scholar 

  277. Linnoila JJ, Binnicker MJ, Majed M, Klein CJ, McKeon A (2016) CSF herpes virus and autoantibody profiles in the evaluation of encephalitis. Neurol Neuroimmunol NeuroInflammation 3:1–10

    Article  Google Scholar 

  278. Danieli D, Moraes ACM, Alves MP, Dutra LA, Höftberger R, Barsottini OGP et al (2017) Anti-N-methyl-D-aspartate receptor encephalitis and Epstein-Barr virus: Another tale on autoimmunity? Eur J Neurol 24:e46–e47

    Article  CAS  Google Scholar 

  279. Dutra LA, Abrantes F, Toso FF, Pedroso JL, Barsottini OGP, Hoftberger R (2018) Autoimmune encephalitis: a review of diagnosis and treatment. Arq Neuropsiquiatr 76:41–49

  280. Granerod J, Ambrose HE, Davies NWS, Clewley JP, Walsh AL, Morgan D et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844

    Article  Google Scholar 

  281. Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA (2012) The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California encephalitis project. Clin Infect Dis 54:899–904

    Article  CAS  Google Scholar 

  282. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12:157–165

    Article  CAS  Google Scholar 

  283. Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA et al (2018) Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 83:166–177

    Article  CAS  Google Scholar 

  284. Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D (2012) Extreme delta brush; a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 79:1094–1100

    Article  Google Scholar 

  285. Balu R, Mccracken L, Lancaster E, Graus F, Dalmau J, Titulaer MJ (2019) A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 92:e244–e252

    Article  Google Scholar 

  286. Van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger KP et al (2016) The clinical spectrum of Caspr2 antibody-associated disease. Neurology 87:521–528

    Article  Google Scholar 

  287. Vale TC, Pedroso JL, Dutra LA, Azevedo L, Filho LHP, Prado LBF et al (2017) Morvan syndrome as a paraneoplastic disorder of thymoma with anti-CASPR2 antibodies. Lancet 389:1367–1368

    Article  Google Scholar 

  288. Lopez-Chiriboga AS, Komorowski L, Kümpfel T, Probst C, Hinson SR, Pittock SJ et al (2016) Metabotropic glutamate receptor type 1 autoimmunity. Neurology 86:1009–1013

    Article  CAS  Google Scholar 

  289. Höftberger R, van Sonderen A, Leypoldt F, Houghton D, Geschwind MD, Gelfand J et al (2015) Encephalitis and AMPA receptor antibodies. Neurology 84:2403–2412

    Article  Google Scholar 

  290. Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega E et al (2014) A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 13:575–586

    Article  CAS  Google Scholar 

  291. Gresa-Arribas N, Planagumà J, Petit-Pedrol M, Kawachi I, Katada S, Glaser CA et al (2016) Human neurexin-3α antibodies associate with encephalitis and alter synapse development. Neurology 86:2235–2242

    Article  CAS  Google Scholar 

  292. Spatola M, Petit-Pedrol M, Simabukuro MM, Armangue T, Castro FJ, Artigues MIB et al (2017) Investigations in GABAA receptor antibody-associated encephalitis. Neurology 88:1012–1020

    Article  CAS  Google Scholar 

  293. Hara M, Ariño H, Petit-Pedrol M, Sabater L, Titulaer MJ, Hernandez EM et al (2017) DPPX antibody-associated encephalitis main syndrome and antibody effects. Neurology 88:1340–1348

    Article  CAS  Google Scholar 

  294. Höftberger R, Titulaer MJ, Sabater L, Dome B, Rózsás A, Hegedus B et al (2013) Encephalitis and GABAB receptor antibodies: Novel findings in a new case series of 20 patients. Neurology 81:1500–1506

    Article  Google Scholar 

  295. Van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, De Bruijn MAAM et al (2016) Anti-LGI1 encephalitis. Neurology 87:1449–1456

    Article  Google Scholar 

  296. Kayser MS, Titulaer MJ, Gresa-Arribas N, Dalmau J (2013) Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-d-aspartate receptor encephalitis. JAMA Neurol 70:1133–1139

    Article  Google Scholar 

  297. Bizzaro N, Tozzoli R, Tonutti E, Piazza A, Manoni F, Ghirardello A et al (1998) Variability between methods to determine ANA, anti-dsDNA and anti-ENA auto antibodies: a collaborative study with the biomedical industry. J Immunol Methods 219:99–107

    Article  CAS  Google Scholar 

  298. Pereira KM, Dellavance A, Andrade LE (2014) The challenge of identification of autoantibodies specific to systemic autoimmune rheumatic diseases in high throughput operation: Proposal of reliable and feasible strategies. J Immunol Methods 437:203–210

    CAS  Google Scholar 

  299. Mummert E, Fritzler MJ, Sjowall C, Bentow C, Mahler M (2018) The clinical utility of anti-double-stranded DNA antibodies and the challenges of their determination. J Immunol Methods 459:11–19

  300. Avrameas S (2016) Autopolyreactivity confers a holistic role in the immune system. Scand J Immunol 83:227–234

    Article  CAS  Google Scholar 

  301. Nagele EP, Han M, Acharya NK, DeMarshall C, Kosciuk MC, Nagele RG (2013) Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS One 8:e60726

  302. Kemeny DM (1991) A practical guide to ELISA. Pergamon Press, Oxford, England

    Google Scholar 

  303. Choi MY, Barber MR, Barber CE, Clarke AE, Fritzler MJ (2016) Preventing the development of SLE: Identifying risk factors and proposing pathways for clinical care. Lupus 25:838–849

    Article  CAS  Google Scholar 

  304. Bossuyt X, Claessens J, Belmondo T, De Langhe E, Westhovens R, Poesen K et al (2019) Harmonization of clinical interpretation of antinuclear antibody test results by solid phase assay and by indirect immunofluorescence through likelihood ratios. Autoimmun Rev 18:102386

  305. Fritzler MJ, Pauls JD, Kinsella TD, Bowen TJ (1985) Antinuclear, anticytoplasmic, and anti-Sjögren’s syndrome antigen A (SS-A/Ro) antibodies in female blood donors. Clin Immunol Immunopathol 36:120–128

    Article  CAS  Google Scholar 

  306. Watanabe A, Kodera M, Sugiura K, Usuda T, Tan EM, Takasaki Y et al (2004) Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 50:892–900

    Article  CAS  Google Scholar 

  307. Dellavance A, Viana VS, Leon EP, Bonfa ES, Andrade LE, Leser PG (2005) The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern. J Rheumatol 32:2144–2149

    CAS  Google Scholar 

  308. Ochs RL, Stein TW Jr, Peebles CL, Gittes RF, Tan EM (1994) Autoantibodies in interstitial cystitis. J Urol 151:587–592

    Article  CAS  Google Scholar 

  309. Ayaki M, Ohoguro N, Azuma N, Majima Y, Yata K, Ibaraki N et al (2002) Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis. Autoimmunity 35:319–327

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    Cristiane Kayser, Edgard Torres dos Reis-Neto, Charlles Heldan de Moura Castro & Luis Eduardo C. Andrade

  2. Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil

    Lívia Almeida Dutra

  3. Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Marvin J. Fritzler

  4. Immunology Division, Fleury Medicine and Health Laboratories, São Paulo, Brazil

    Luis Eduardo C. Andrade

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Kayser, C., Dutra, L.A., dos Reis-Neto, E.T. et al. The Role of Autoantibody Testing in Modern Personalized Medicine. Clinic Rev Allerg Immunol 63, 251–288 (2022). https://doi.org/10.1007/s12016-021-08918-6

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