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The Clinical Aspects of Autoantibodies

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Scleroderma

Abstract

Since clinical presentation in patients with systemic sclerosis (SSc) is highly heterogeneous, disease subgrouping and prediction of future organ involvement and prognosis are extremely important in the clinical setting. Another distinctive feature of SSc is the presence of circulating autoantibodies reactive with various cellular components. Autoimmune targets include a variety of nuclear antigens that are present in cells with nuclei. In this case, they are termed antinuclear antibodies (ANAs). It has been shown that distinct ANA specificities are detected in SSc patients and are associated with unique disease manifestations. Therefore, SSc-related ANAs are attractive biomarkers in routine rheumatology practice, owing to their high specificity, mutual exclusivity, persistence for the duration of illness, and, most importantly, strong associations with characteristic constellations of clinical features. In addition, a new group of autoantibodies reactive with functional proteins, such as cell surface receptors and extracellular matrix (ECM) proteins, have been identified in SSc patients. They seem to directly activate pathways that may contribute to the pathophysiology of SSc. This chapter covers the spectrum of autoantibody specificities reported in SSc patients, their detection methods, and their clinical utility.

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References

  1. Okano Y. Antinuclear antibody in systemic sclerosis (scleroderma). Rheum Dis Clin North Am. 1996;22(4):709–35.

    Article  CAS  PubMed  Google Scholar 

  2. Hamaguchi Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37(1):42–53.

    Article  CAS  PubMed  Google Scholar 

  3. Mehra S, Walker J, Patterson K, Fritzler MJ. Autoantibodies in systemic sclerosis. Autoimmun Rev. 2013;12(3):340–54.

    Article  CAS  PubMed  Google Scholar 

  4. Moroi Y, Peebles C, Fritzler MJ, Steigerwald J, Tan EM. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci U S A. 1980;77(3):1627–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gelber AC, Pillemer SR, Baum BJ, Wigley FM, Hummers LK, Morris S, et al. Distinct recognition of antibodies to centromere proteins in primary Sjogren’s syndrome compared with limited scleroderma. Ann Rheum Dis. 2006;65(8):1028–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Senecal JL, Dieudé M, Koenig M. Predictive value of antinuclear autoantibodies: the lessons of the systemic sclerosis autoantibodies. Autoimmun Rev. 2008;7(8):588–93.

    Article  PubMed  CAS  Google Scholar 

  7. Steen VD, Powell DL, Medsger Jr TA. Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum. 1988;31(2):196–203.

    Article  CAS  PubMed  Google Scholar 

  8. Kuwana M, Kaburaki J, Okano Y, Tojo T, Homma M. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum. 1994;37(1):75–83.

    Article  CAS  PubMed  Google Scholar 

  9. Douvas AS, Achten M, Tan EM. Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. J Biol Chem. 1979;254(20):10514–22.

    CAS  PubMed  Google Scholar 

  10. Shero JH, Bordwell B, Rothfield NF, Earnshaw WC. High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science. 1986;231(4739):737–40.

    Article  CAS  PubMed  Google Scholar 

  11. Domsic RT, Rodriguez-Reyna T, Lucas M, Fertig N, Medsger Jr TA. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis. 2011;70(1):104–9.

    Article  PubMed  Google Scholar 

  12. Perera A, Fertig N, Lucas M, Rodriguez-Reyna TS, Hu P, Steen VD, Medsger Jr TA. Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. Arthritis Rheum. 2007;56(8):2740–6.

    Article  PubMed  Google Scholar 

  13. Kuwana M, Kaburaki J, Mimori T, Tojo T, Homma M. Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis. J Clin Invest. 1993;91(4):1399–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kuwana M, Okano Y, Kaburaki J, Medsger Jr TA, Wright TM. Autoantibodies to RNA polymerases recognize multiple subunits and demonstrate cross-reactivity with RNA polymerase complexes. Arthritis Rheum. 1999;42(2):275–84.

    Article  CAS  PubMed  Google Scholar 

  15. Satoh M, Kuwana M, Ogasawara T, Ajmani AK, Langdon JJ, Kimpel D, et al. Association of autoantibodies to topoisomerase I and the phosphorylated (IIO) form of RNA polymerase II in Japanese scleroderma patients. J Immunol. 1994;153(12):5838–48.

    CAS  PubMed  Google Scholar 

  16. Kuwana M, Okano Y, Kaburaki J, Tojo T, Medsger Jr TA. Racial differences in the distribution of systemic sclerosis-related serum antinuclear antibodies. Arthritis Rheum. 1994;37(6):902–6.

    Article  CAS  PubMed  Google Scholar 

  17. Meyer OC, Fertig N, Lucas M, Somogyi N, Medsger Jr TA. Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis. J Rheumatol. 2007;34(1):104–9.

    PubMed  Google Scholar 

  18. Okano Y, Steen VD, Medsger Jr TA. Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med. 1993;119(10):1005–13.

    Article  CAS  PubMed  Google Scholar 

  19. Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  20. Shah AA, Rosen A, Hummers L, Wigley F, Casciola-Rosen L. Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum. 2010;62(9):2787–95.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Moinzadeh P, Fonseca C, Hellmich M, Shah AA, Chighizola C, Denton CP, Ong VH. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther. 2014;16(1):R53.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lischwe MA, Ochs RL, Reddy R, Cook RG, Yeoman LC, Tan EM, et al. Purification and partial characterization of a nucleolar scleroderma antigen (Mr = 34,000; pI, 8.5) rich in NG, NG-dimethylarginine. J Biol Chem. 1985;260(26):14304–10.

    CAS  PubMed  Google Scholar 

  23. Aggarwal R, Lucas M, Fertig N, Oddis CV, Medsger Jr TA. Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum. 2009;60(4):1112–8.

    Article  PubMed  Google Scholar 

  24. Gündüz OH, Fertig N, Lucas M, Medsger Jr TA. Systemic sclerosis with renal crisis and pulmonary hypertension: a report of eleven cases. Arthritis Rheum. 2001;44(7):1663–6.

    Article  PubMed  Google Scholar 

  25. Van Eenennaam H, Vogelzangs JH, Lugtenberg D, Van Den Hoogen FH, Van Venrooij WJ, Pruijn GJ. Identity of the RNase MRP- and RNase P-associated Th/To autoantigen. Arthritis Rheum. 2002;46(12):3266–72.

    Article  PubMed  CAS  Google Scholar 

  26. Mitri GM, Lucas M, Fertig N, Steen VD, Medsger Jr TA. A comparison between anti-Th/To-and anticentromere antibody-positive systemic sclerosis patients with limited cutaneous involvement. Arthritis Rheum. 2003;48(1):203–9.

    Article  PubMed  Google Scholar 

  27. Fertig N, Domsic RT, Rodriguez-Reyna T, Kuwana M, Lucas M, Medsger Jr TA, et al. Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis Rheum. 2009;61(7):958–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reimer G, Scheer U, Peters JM, Tan EM. Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/scleroderma overlap syndromes. J Immunol. 1986;137(12):3802–8.

    CAS  PubMed  Google Scholar 

  29. Koschik 2nd RW, Fertig N, Lucas MR, Domsic RT, Medsger Jr TA. Anti-PM-Scl antibody in patients with systemic sclerosis. Clin Exp Rheumatol. 2012;30(2 Suppl 71):S12–6.

    PubMed  Google Scholar 

  30. D’Aoust J, Hudson M, Tatibouet S, Wick J, Mahler M, Baron M, Fritzler MJ, Canadian Scleroderma Research Group. Clinical and serologic correlates of anti-PM/Scl antibodies in systemic sclerosis: a multicenter study of 763 patients. Arthritis Rheumatol. 2014;66(6):1608–15.

    Article  PubMed  CAS  Google Scholar 

  31. Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, et al. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001;60(2):116–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest. 1981;68(3):611–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cavazzana I, Fredi M, Taraborelli M, Quinzanini M, Tincani A, Franceschini F. A subset of systemic sclerosis but not of systemic lupus erythematosus is defined by isolated anti-Ku autoantibodies. Clin Exp Rheumatol. 2013;31(2 Suppl 76):118–21.

    PubMed  Google Scholar 

  34. Rozman B, Cucnik S, Sodin-Semrl S, Czirjak L, Varju C, Distler O, et al. Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study. Ann Rheum Dis. 2008;67(9):1282–6.

    Article  CAS  PubMed  Google Scholar 

  35. Kaji K, Fertig N, Medsger Jr TA, Satoh T, Hoshino K, Hamaguchi Y, et al. Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. Arthritis Care Res (Hoboken). 2014;66(4):575–84.

    Article  CAS  Google Scholar 

  36. Pettersson I, Hinterberger M, Mimori T, Gottlieb E, Steitz JA. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem. 1984;259(9):5907–14.

    CAS  PubMed  Google Scholar 

  37. Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972;52(2):148–59.

    Article  CAS  PubMed  Google Scholar 

  38. Gunnarsson R, Andreassen AK, Molberg Ø, Lexberg ÅS, Time K, Dhainaut AS, et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatology (Oxford). 2013;52(7):1208–13.

    Article  CAS  Google Scholar 

  39. Rodriguez-Sanchez JL, Gelpi C, Juarez C, Hardin JA. A new autoantibody in scleroderma that recognizes a 90-kDa component of the nucleolus-organizing region of chromatin. J Immunol. 1987;139(8):2579–84.

    CAS  PubMed  Google Scholar 

  40. Dagher JH, Scheer U, Voit R, Grummt I, Lonzetti L, Raymond Y, et al. Autoantibodies to NOR 90/hUBF: longterm clinical and serological followup in a patient with limited systemic sclerosis suggests an antigen driven immune response. J Rheumatol. 2002;29(7):1543–7.

    PubMed  Google Scholar 

  41. Ulanet DB, Wigley FM, Gelber AC, Rosen A. Autoantibodies against B23, a nucleolar phosphoprotein, occur in scleroderma and are associated with pulmonary hypertension. Arthritis Rheum. 2003;49(1):85–92.

    Article  PubMed  Google Scholar 

  42. Hudson M, Pope J, Mahler M, Tatibouet S, Steele R, Baron M, et al. Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis. Arthritis Res Ther. 2012;14(2):R50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Costa S, Mondini M, Caneparo V, Afeltra A, Airò P, Bellisai F, et al. Detection of anti-IFI16 antibodies by ELISA: clinical and serological associations in systemic sclerosis. Rheumatology (Oxford). 2011;50(4):674–81.

    Article  CAS  Google Scholar 

  44. Cavazzana I, Ceribelli A, Taraborelli M, Fredi M, Norman G, Tincani A, et al. Primary biliary cirrhosis-related autoantibodies in a large cohort of Italian patients with systemic sclerosis. J Rheumatol. 2011;38(10):2180–5.

    Article  PubMed  Google Scholar 

  45. Salazar GA, Assassi S, Wigley F, Hummers L, Varga J, Hinchcliff M, et al. Antinuclear antibody-negative systemic sclerosis. Semin Arthritis Rheum. 2014. doi:10.1016/j.semarthrit.2014.11.006 [Epub ahead of print].

    PubMed  PubMed Central  Google Scholar 

  46. Shanmugam VK, Swistowski DR, Saddic N, Wang H, Steen VD. Comparison of indirect immunofluorescence and multiplex antinuclear antibody screening in systemic sclerosis. Clin Rheumatol. 2011;30(10):1363–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Damoiseaux J, Boesten K, Giesen J, Austen J, Tervaert JW. Evaluation of a novel line-blot immunoassay for the detection of antibodies to extractable nuclear antigens. Ann N Y Acad Sci. 2005;1050(6):340–7.

    Article  CAS  PubMed  Google Scholar 

  48. Kuwana M, Kimura K, Kawakami Y. Identification of an immunodominant epitope on RNA polymerase III recognized by systemic sclerosis sera: application to enzyme-linked immunosorbent assay. Arthritis Rheum. 2002;46(10):2742–7.

    Article  CAS  PubMed  Google Scholar 

  49. Op De Beéck K, Vermeersch P, Verschueren P, Westhovens R, Mariën G, Blockmans D, et al. Antinuclear antibody detection by automated multiplex immunoassay in untreated patients at the time of diagnosis. Autoimmun Rev. 2012;12(2):137–43.

    Article  PubMed  CAS  Google Scholar 

  50. Baroni SS, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006;354(25):2667–76.

    Article  CAS  PubMed  Google Scholar 

  51. Singh J, Mehendiratta V, Del Galdo F, Jimenez SA, Cohen S, et al. Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2009;297(6):G1206–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kawaguchi Y, Nakamura Y, Matsumoto I, Nishimagi E, Satoh T, Kuwana M, et al. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann Rheum Dis. 2009;68(5):710–4.

    Article  CAS  PubMed  Google Scholar 

  53. Riemekasten G, Philippe A, Näther M, Slowinski T, Müller DN, Heidecke H, et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis. 2011;70(3):530–6.

    Article  CAS  PubMed  Google Scholar 

  54. Tan FK, Arnett FC, Antohi S, Saito S, Mirarchi A, Spiera H, et al. Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. J Immunol. 1999;163(2):1066–72.

    CAS  PubMed  Google Scholar 

  55. Sato S, Hayakawa M, Hasegawa M, Fujimoto M, Takehara K. Function blocking autoantibodies against matrix metalloproteinase-1 patients with systemic sclerosis. J Invest Dermatol. 2003;120(4):542–7.

    Article  CAS  PubMed  Google Scholar 

  56. Nishijima C, Hayakawa I, Matsushita T, Komura K, Hasegawa M, Takehara K. Autoantibody against matrix metalloproteinase-3 patients with systemic sclerosis. Clin Exp Immunol. 2004;138(2):357–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Iwata Y, Ogawa F, Komura K, Muroi E, Hara T, Shimizu K, et al. Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress. Rheumatology (Oxford). 2007;46(5):790–5.

    Article  CAS  Google Scholar 

  58. Ogawa F, Shimizu K, Hara T, Muroi E, Komura K, Takenaka M, et al. Autoantibody against one of the antioxidant repair enzymes, methionine sulfoxide reductase A, in systemic sclerosis: association with pulmonary fibrosis and vascular damage. Arch Dermatol Res. 2010;302(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  59. Grader-Beck T, Boin F, von Gunten S, Smith D, Rosen A, Bochner BS. Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease. Ann Rheum Dis. 2011;70(12):2218–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Giovannetti A, Maselli A, Colasanti T, Rosato E, Salsano F, Pisarri S, et al. Autoantibodies to estrogen receptor α in systemic sclerosis (SSc) as pathogenetic determinants and markers of progression. PLoS One. 2013;8(9):e74332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2734–47.

    Google Scholar 

  62. Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008;58(12):3902–12.

    Article  PubMed  Google Scholar 

  63. Matucci-Cerinic M, Allanore Y, Czirják L, Tyndall A, Müller-Ladner U, Denton C, et al. The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy. Ann Rheum Dis. 200968(9):1377–80.

    Google Scholar 

  64. Scalapino K, Arkachaisri T, Lucas M, Fertig N, Helfrich DJ, Londino Jr AV, et al. Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. J Rheumatol. 2006;33(5):1004–13.

    PubMed  Google Scholar 

  65. Martini G, Foeldvari I, Russo R, Cuttica R, Eberhard A, Ravelli A, et al. Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database. Arthritis Rheum. 2006;54(12):3971–8.

    Article  CAS  PubMed  Google Scholar 

  66. Reveille JD, Fischbach M, McNearney T, Friedman AW, Aguilar MB, Lisse J, et al. Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum. 2001;30(5):332–46.

    Article  CAS  PubMed  Google Scholar 

  67. Krzyszczak ME, Li Y, Ross SJ, Ceribelli A, Chan EK, Bubb MR, et al. Gender and ethnicity differences in the prevalence of scleroderma-related autoantibodies. Clin Rheumatol. 2011;30(10):1333–9.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ceribelli A, Cavazzana I, Franceschini F, Airò P, Tincani A, Cattaneo R, et al. Anti-Th/To are common antinucleolar autoantibodies in Italian patients with scleroderma. J Rheumatol. 2010;37(10):2071–5.

    Article  CAS  PubMed  Google Scholar 

  69. Panicheewa S, Chitrabamrung S, Verasertniyom O, Vanichaphantu M, Kraisit SO, Chiewsilp P, et al. Diffuse systemic sclerosis and related diseases in Thailand. Clin Rheumatol. 1991;10(2):124–9.

    Article  CAS  PubMed  Google Scholar 

  70. Sobanski V, Dauchet L, Lefèvre G, Lambert M, Morell-Dubois S, Sy T, et al. Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: new data from a French cohort and a systematic review and meta-analysis. Arthritis Rheumatol. 2014;66(2):407–17.

    Article  CAS  PubMed  Google Scholar 

  71. Arnett FC, Howard RF, Tan F, Moulds JM, Bias WB, Durban E, et al. Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma Association with an Amerindian HLA haplotype. Arthritis Rheum. 1996;39(8):1362–70.

    Article  CAS  PubMed  Google Scholar 

  72. Moinzadeh P, Aberer E, Ahmadi-Simab K, Blank N, Distler JH, Fierlbeck G, et al. Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2015;74(4):730–7.

    Article  CAS  PubMed  Google Scholar 

  73. Reveille JD, Solomon DH. Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl-70, and nucleolar antibodies. Arthritis Rheum. 2003;49(3):399–412.

    Article  PubMed  Google Scholar 

  74. Hanke K, Dahnrich C, Bruckner CS, Huscher D, Becker M, Jansen A, et al. Diagnostic value of anti-topoisomerase I antibodies in a large monocentric cohort. Arthritis Res Ther. 2009;11(1):R28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Scussel-Lonzetti L, Joyal F, Raynauld JP, Roussin A, Rich E, Goulet JR, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002;81(2):154–67.

    Article  Google Scholar 

  76. Meyer O, De Chaisemartin L, Nicaise-Roland P, Cabane J, Tubach F, Dieude P, Allanore Y, et al. Anti-RNA polymerase III antibody prevalence and associated clinical manifestations in a large series of French patients with systemic sclerosis: a cross-sectional study. J Rheumatol. 2010;37(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  77. Cavazzana I, Angela C, Paolo A, Stefania Z, Angela T, Franco F. Anti-RNA polymerase III antibodies: a marker of systemic sclerosis with rapid onset and skin thickening progression. Autoimmun Rev. 2009;8(7):580–4.

    Article  CAS  PubMed  Google Scholar 

  78. Poormoghim H, Lucas M, Fertig N, Medsger Jr TA. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum. 2000;43(2):444–51.

    Article  CAS  PubMed  Google Scholar 

  79. Toya SP, Tzelepis GE. The many faces of scleroderma sine scleroderma: a literature review focusing on cardiopulmonary complications. Rheumatol Int. 2009;29(8):861–8.

    Article  PubMed  Google Scholar 

  80. Fischer A, Pfalzgraf FJ, Feghali-Bostwick CA, Wright TM, Curran-Everett D, West SG, et al. Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis. J Rheumatol. 2006;33(8):1600–5.

    PubMed  Google Scholar 

  81. Fischer A, Meehan RT, Feghali-Bostwick CA, West SG, Brown KK. Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease. Chest. 2006;130(4):976–81.

    Article  PubMed  Google Scholar 

  82. Okano Y, Medsger Jr TA. Autoantibody to Th ribonucleoprotein (nucleolar 7–2 RNA protein particle) in patients with systemic sclerosis. Arthritis Rheum. 1990;33(12):1822–8.

    Article  CAS  PubMed  Google Scholar 

  83. Generini S, Steiner G, Miniati I, Conforti ML, Guiducci S, Skriner K, et al. Anti-hnRNP and other autoantibodies in systemic sclerosis with joint involvement. Rheumatology (Oxford). 2009;48(8):920–5.

    Article  CAS  Google Scholar 

  84. Sharif R, Fritzler MJ, Mayes MD, Gonzalez EB, McNearney TA, Draeger H, et al. Anti-fibrillarin antibody in African American patients with systemic sclerosis: immunogenetics, clinical features, and survival analysis. J Rheumatol. 2011;38(8):1622–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Nishimagi E, Tochimoto A, Kawaguchi Y, Satoh T, Kuwana M, Takagi K, et al. Characteristics of patients with early systemic sclerosis and severe gastrointestinal tract involvement. J Rheumatol. 2007;34(10):2050–5.

    PubMed  Google Scholar 

  86. Ghrénassia E, Avouac J, Khanna D, Derk CT, Distler O, Suliman YA, et al. Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study. J Rheumatol. 2014;41(1):99–105.

    Article  PubMed  Google Scholar 

  87. Hung EW, Mayes MD, Sharif R, Assassi S, Machicao VI, Hosing C, et al. Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial. J Rheumatol. 2013;40(4):455–60.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Penn H, Howie AJ, Kingdon EJ, Bunn CC, Stratton RJ, Black CM, et al. Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM. 2007;100(8):485–94.

    Article  CAS  PubMed  Google Scholar 

  89. Hamaguchi Y, Kodera M, Matsushita T, Hasegawa M, Inaba Y, Usuda T, et al. Clinical and immunological predictors of scleroderma renal crisis for Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies. Arthritis Rheumatol. 2014. doi:10.1002/art.38994 [Epub ahead of print].

    PubMed  PubMed Central  Google Scholar 

  90. Codullo V, Cavazzana I, Bonino C, Alpini C, Cavagna L, Cozzi F, et al. Serologic profile and mortality rates of scleroderma renal crisis in Italy. J Rheumatol. 2009;36(7):1464–9.

    Article  PubMed  Google Scholar 

  91. Bhavsar SV, Carmona R. Anti-RNA polymerase III antibodies in the diagnosis of scleroderma renal crisis in the absence of skin disease. J Clin Rheumatol. 2014;20(7):379–82.

    PubMed  Google Scholar 

  92. Steen V, Medsger Jr TA. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003;48(2):516–22.

    Article  PubMed  Google Scholar 

  93. Coghlan JG, Denton CP, Grünig E, Bonderman D, Distler O, Khanna D, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–9.

    Article  PubMed  Google Scholar 

  94. Blanco I, Mathai S, Shafiq M, Boyce D, Kolb TM, Chami H, et al. Severity of systemic sclerosis-associated pulmonary arterial hypertension in African Americans. Medicine (Baltimore). 2014;93(5):177–85.

    Article  Google Scholar 

  95. Steen VD, Lucas M, Fertig N, Medsger Jr TA. Pulmonary arterial hypertension and severe pulmonary fibrosis in systemic sclerosis patients with a nucleolar antibody. J Rheumatol. 2007;34(11):2230–5.

    CAS  PubMed  Google Scholar 

  96. Becker MO, Kill A, Kutsche M, Guenther J, Rose A, Tabeling C, et al. Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis. Am J Respir Crit Care Med. 2014;190(7):808–17.

    Article  CAS  PubMed  Google Scholar 

  97. McNearney TA, Reveille JD, Fischbach M, Friedman AW, Lisse JR, Goel N, et al. Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors. Arthritis Rheum. 2007;57(2):318–26.

    Article  PubMed  Google Scholar 

  98. Higuchi M, Horiuchi T, Ishibashi N, Yoshizawa S, Niho Y, Nagasawa K. Anticentromere antibody as a risk factor for cancer in patients with systemic sclerosis. Clin Rheumatol. 2000;19(2):123–6.

    Article  CAS  PubMed  Google Scholar 

  99. Rothfield N, Kurtzman S, Vazques-Abad D, Charron C, Daniels L, Greenberg B. Association of anti-topoisomerase I with cancer. Arthritis Rheum. 1992;35(6):724.

    Article  CAS  PubMed  Google Scholar 

  100. Shah AA, Hummers LK, Casciola-Rosen L, Visvanathan K, Rosen A, Wigley FM. Examination of autoantibody status and clinical features that associate with cancer risk and cancer-associated scleroderma. Arthritis Rheumatol. 2015. doi:10.1002/art.39022 [Epub ahead of print].

    Google Scholar 

  101. Jacobsen S, Ullman S, Shen GQ, Wiik A, Halberg P. Influence of clinical features, serum antinuclear antibodies, and lung function on survival of patients with systemic sclerosis. J Rheumatol. 2001;28(11):2454–9.

    CAS  PubMed  Google Scholar 

  102. Hu PQ, Fertig N, Medsger Jr TA, Wright TM. Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis Rheum. 2003;48(5):1363–73.

    Article  CAS  PubMed  Google Scholar 

  103. Kuwana M, Kaburaki J, Mimori T, Kawakami Y, Tojo T. Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis. Arthritis Rheum. 2000;43(5):1074–84.

    Article  CAS  PubMed  Google Scholar 

  104. Kuwana M, Okano Y, Pandey JP, Silver RM, Fertig N, Medsger Jr TA. Enzyme-linked immunosorbent assay for detection of anti-RNA polymerase III antibody: analytical accuracy and clinical associations in systemic sclerosis. Arthritis Rheum. 2005;52(8):2425–32.

    Article  CAS  PubMed  Google Scholar 

  105. Nihtyanova SI, Parker JC, Black CM, Bunn CC, Denton CP. A longitudinal study of anti-RNA polymerase III antibody levels in systemic sclerosis. Rheumatology (Oxford). 2009;48(10):1218–21.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan

    Masataka Kuwana MD, PhD

  2. Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Thomas A. Medsger Jr. MD

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  1. Masataka Kuwana MD, PhD
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  2. Thomas A. Medsger Jr. MD
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Correspondence to Masataka Kuwana MD, PhD .

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Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

    John Varga

  2. Division of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, UCL Division of Medicine, Royal Free Hospital, London, United Kingdom

    Christopher P. Denton

  3. Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA

    Fredrick M. Wigley

  4. Service de Rhumatologie A, INSERMU1016, Universit. Paris Descartes, Hôpital Cochin, Paris, France

    Yannick Allanore

  5. Department of Allergy and Rheumatology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan

    Masataka Kuwana

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Kuwana, M., Medsger, T.A. (2017). The Clinical Aspects of Autoantibodies. In: Varga, J., Denton, C., Wigley, F., Allanore, Y., Kuwana, M. (eds) Scleroderma. Springer, Cham. https://doi.org/10.1007/978-3-319-31407-5_15

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  • DOI: https://doi.org/10.1007/978-3-319-31407-5_15

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