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Cutting-edge Issues in Autoimmunity and Allergy of the Digestive System

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Abstract

Autoimmunity and allergy involving the digestive system may be considered as paradigmatic for numerous common themes of complex diseases secondary to tolerance breakdown. Among gastrointestinal autoimmune diseases, for example, we encounter diseases in which a clear environmental trigger is identified (i.e., celiac disease), serum autoantibodies are most specific (i.e., primary biliary cirrhosis), or in which the disease pathophysiology is clearly understood (i.e., autoimmune gastritis). Similarly, it is intriguing that the gastrointestinal tract and the liver circulation represent the crucial environment for the development of immune tolerance. This issue is dedicated to the discussion of recent concepts while identifying two major common issues, i.e., the need for serum biomarkers and the role of vitamin D. Other common themes characterize the etiology and effector mechanisms of these and other autoimmune diseases and are discussed in each cutting-edge overview.

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References

  1. Gershwin ME, Shoenfeld Y (2011) Cutting-edge issues in organ-specific autoimmunity. Clin Rev Allergy Immunol 41:123–125

    Article  PubMed  CAS  Google Scholar 

  2. Gorlova O, Martin JE, Rueda B, Koeleman BP, Ying J, Teruel M et al (2011) Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy. PLoS genet 7:e1002178

    Article  PubMed  CAS  Google Scholar 

  3. Allanore Y, Saad M, Dieude P, Avouac J, Distler JH, Amouyel P et al (2011) Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS genet 7:e1002091

    Article  PubMed  CAS  Google Scholar 

  4. Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R et al (2010) Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet 42:426–429

    Article  PubMed  CAS  Google Scholar 

  5. Deng Y, Tsao BP (2010) Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol 6:683–692

    Article  PubMed  CAS  Google Scholar 

  6. Wang S, Adrianto I, Wiley GB, Lessard CJ, Kelly JA, Adler AJ et al. (2012) A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus. Genes Immun. doi:10.1038/gene.2012.6

  7. Lessard CJ, Adrianto I, Ice JA, Wiley GB, Kelly JA, Glenn SB et al (2012) Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study. Am J Hum Genet 90:648–660

    Article  PubMed  CAS  Google Scholar 

  8. Mells GF, Floyd JA, Morley KI, Cordell HJ, Franklin CS, Shin SY et al (2011) Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 43:329–332

    Article  PubMed  CAS  Google Scholar 

  9. Liu X, Invernizzi P, Lu Y, Kosoy R, Bianchi I, Podda M et al (2010) Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 42:658–660

    Article  PubMed  CAS  Google Scholar 

  10. Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A et al (2012) Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nature Genet 44(5):511–516

    Article  PubMed  CAS  Google Scholar 

  11. Terao C, Ohmura K, Katayama M, Takahashi M, Kokubo M, Diop G et al (2011) Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis—a genome-wide study combined with immunological analyses. PLoS One 6:e20457

    Article  PubMed  CAS  Google Scholar 

  12. Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L et al (2011) Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS genet 7:e1002004

    Article  PubMed  CAS  Google Scholar 

  13. Eyre S, Ke X, Lawrence R, Bowes J, Panoutsopoulou K, Barton A et al (2011) Examining the overlap between genome-wide rare variant association signals and linkage peaks in rheumatoid arthritis. Arthritis rheum 63:1522–1526

    Article  PubMed  CAS  Google Scholar 

  14. Liu C, Ackerman HH, Carulli JP (2011) A genome-wide screen of gene-gene interactions for rheumatoid arthritis susceptibility. Hum Genet 129:473–485

    Article  PubMed  Google Scholar 

  15. Padyukov L, Seielstad M, Ong RT, Ding B, Ronnelid J, Seddighzadeh M et al (2011) A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Ann Rheum Dis 70:259–265

    Article  PubMed  Google Scholar 

  16. Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG et al (2011) Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum 63:645–653

    Article  PubMed  CAS  Google Scholar 

  17. Festen EA, Goyette P, Green T, Boucher G, Beauchamp C, Trynka G et al (2011) A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn’s disease and celiac disease. PLoS genet 7:e1001283

    Article  PubMed  CAS  Google Scholar 

  18. Smyk D, Rigopoulou EI, Baum H, Burroughs AK, Vergani D, Bogdanos DP (2012) Autoimmunity and environment: am I at risk? Clin rev allergy immunol 42:199–212

    Article  PubMed  CAS  Google Scholar 

  19. Ramos PS, Criswell LA, Moser KL, Comeau ME, Williams AH, Pajewski NM et al (2011) A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS genet 7:e1002406

    Article  PubMed  CAS  Google Scholar 

  20. Bogdanos DP, Smyk DS, Rigopoulou EI, Mytilinaiou MG, Heneghan MA, Selmi C et al (2012) Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun 38:J156–J169

    Article  PubMed  Google Scholar 

  21. Brooks WH (2012) Mechanisms and pathophysiology of autoimmune disease. Clin rev allergy immunol 42:1–4

    Article  PubMed  CAS  Google Scholar 

  22. Misery L (2011) Atopic dermatitis: new trends and perspectives. Clin rev allergy immunol 41:296–297

    Article  PubMed  Google Scholar 

  23. Valesini G, Conti F (2011) The persistent challenge of lupus nephritis. Clin rev allergy immunol 40:135–137

    Article  PubMed  Google Scholar 

  24. Selmi C (2011) Novel challenges for the allergist. Clin rev allergy immunol 41:1–3

    Article  PubMed  Google Scholar 

  25. Guillevin L (2011) A contemporary update on scleroderma. Clin rev allergy immunol 40:75–77

    Article  PubMed  Google Scholar 

  26. Peeva E (2011) Reproductive immunology: a focus on the role of female sex hormones and other gender-related factors. Clin rev allergy immunol 40:1–7

    Article  PubMed  CAS  Google Scholar 

  27. Bizzaro N, Tozzoli R, Villalta D, Fabris M, Tonutti E (2012) Cutting-edge issues in celiac disease and in gluten intolerance. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8223-1

  28. Folci M, Meda F, Gershwin ME, Selmi C (2012) Cutting-edge issues in primary biliary cirrhosis. Clin Rev Allergy Immunol. doi:10.1007/s12016-011-8253-3

  29. Toh BH, Chan J, Kyaw T, Alderuccio F (2012) Cutting edge issues in autoimmune gastritis. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8218-y

  30. Vergani D, Mieli-Vergani G (2012) Cutting edge issues in autoimmune hepatitis. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8236-9

  31. Hajeb P, Selamat J (2012) A contemporary review of seafood allergy. Clin Rev Allergy Immunol. doi:10.1007/s12016-011-8284-9

  32. Nussinovitch U, Shoenfeld Y (2012) The diagnostic and clinical significance of anti-muscarinic receptor autoantibodies. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8235-x

  33. Bonaguri C, Melegari A, Ballabio A, Parmeggiani M, Russo A, Battistelli L et al (2011) Italian multicentre study for application of a diagnostic algorithm in autoantibody testing for autoimmune rheumatic disease: conclusive results. Autoimmun Rev 11:1–5

    Article  PubMed  Google Scholar 

  34. Conrad K, Roggenbuck D, Reinhold D, Sack U (2012) Autoantibody diagnostics in clinical practice. Autoimmun Rev 11:207–211

    Article  PubMed  CAS  Google Scholar 

  35. Hickman-Brecks CL, Racz JL, Meyer DM, LaBranche TP, Allen PM (2011) Th17 cells can provide B cell help in autoantibody induced arthritis. J Autoimmun 36:65–75

    Article  PubMed  CAS  Google Scholar 

  36. Hu N, Westra J, Kallenberg CG (2011) Dysregulated neutrophil–endothelial interaction in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: implications for pathogenesis and disease intervention. Autoimmun Rev 10:536–543

    Article  PubMed  Google Scholar 

  37. Somers K, Geusens P, Elewaut D, De Keyser F, Rummens JL, Coenen M et al (2011) Novel autoantibody markers for early and seronegative rheumatoid arthritis. J Autoimmun 36:33–46

    Article  PubMed  CAS  Google Scholar 

  38. Rozenberg O, Lerner A, Pacht A, Grinberg M, Reginashvili D, Henig C et al. (2012) A novel algorithm for the diagnosis of celiac disease and a comprehensive review of celiac disease diagnostics. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8250-y

  39. Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, et al. (2012) Overcoming a “probable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8234-y

  40. Selmi C, Bowlus CL, Gershwin ME, Coppel RL (2011) Primary biliary cirrhosis. Lancet 377:1600–1609

    Article  PubMed  CAS  Google Scholar 

  41. Mytilinaiou MG, Meyer W, Scheper T, Rigopoulou EI, Probst C, Koutsoumpas AL et al. (2012) Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis. Clin Chim Acta. doi:10.1016/j.cca.2012.03.020

  42. Selmi C, Meroni PL, Gershwin ME (2012) Primary biliary cirrhosis and Sjogren’s syndrome: autoimmune epithelitis. J Autoimmun. doi:10.1016/j.jaut.2011.11.005

  43. Shapira Y, Agmon-Levin N, Shoenfeld Y (2010) Defining and analyzing geoepidemiology and human autoimmunity. J Autoimmun 34:J168–J177

    Article  PubMed  CAS  Google Scholar 

  44. Antico A, Tozzoli R, Giavarina D, Tonutti E, Bizzaro N (2012) Hypovitaminosis D as predisposing factor for atrophic type A gastritis: a case–control study and review of the literature on the interaction of vitamin D with the immune system. Clin Rev Allergy Immunol. doi:10.1007/s12016-011-8255-1

  45. Lerner A, Shapira Y, Agmon-Levin N, Pacht A, Ben-Ami Shor D, Lopez HM et al. (2012) The clinical significance of 25OH-vitamin D status in celiac disease. Clin Rev Allergy Immunol. doi:10.1007/s12016-010-8237-8

  46. Arnson Y, Amital H, Agmon-Levin N, Alon D, Sanchez-Castanon M, Lopez-Hoyos M et al (2011) Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev 10:490–494

    Article  PubMed  CAS  Google Scholar 

  47. Cutolo M, Pizzorni C, Sulli A (2011) Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev 11:84–87

    Article  PubMed  CAS  Google Scholar 

  48. Hajas A, Sandor J, Csathy L, Csipo I, Barath S, Paragh G et al (2011) Vitamin D insufficiency in a large MCTD population. Autoimmun Rev 10:317–324

    Article  PubMed  CAS  Google Scholar 

  49. Invernizzi P (2010) Geoepidemiology of autoimmune liver diseases. J Autoimmun 34:J300–J306

    Article  PubMed  CAS  Google Scholar 

  50. Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:J314–J321

    Article  PubMed  CAS  Google Scholar 

  51. Zeki AA, Schivo M, Chan AL, Hardin KA, Kenyon NJ, Albertson TE et al (2010) Geoepidemiology of COPD and idiopathic pulmonary fibrosis. J Autoimmun 34:J327–J338

    Article  PubMed  CAS  Google Scholar 

  52. Shoenfeld Y, Selmi C, Zimlichman E, Gershwin ME (2008) The autoimmunologist: geoepidemiology, a new center of gravity, and prime time for autoimmunity. J Autoimmun 31:325–330

    Article  PubMed  Google Scholar 

  53. Moroni L, Bianchi I, Lleo A (2012) Geoepidemiology, gender and autoimmune disease. Autoimmun Rev 11:A386–A392

    Article  PubMed  Google Scholar 

  54. Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Tervaert JW et al (2011) Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev 10:733–743

    Article  PubMed  CAS  Google Scholar 

  55. Hypponen E (2010) Vitamin D and increasing incidence of type 1 diabetes—evidence for an association? Diabetes Obes Metab 12:737–743

    Article  PubMed  CAS  Google Scholar 

  56. Selmi C, Tsuneyama K (2010) Nutrition, geoepidemiology, and autoimmunity. Autoimmun Rev 9:A267–A270

    Article  PubMed  CAS  Google Scholar 

  57. Zold E, Szodoray P, Nakken B, Barath S, Kappelmayer J, Csathy L et al (2011) Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease. Autoimmun Rev 10:155–162

    Article  PubMed  CAS  Google Scholar 

  58. Adorini L, Penna G (2009) Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D receptor agonists. Hum Immunol 70:345–352

    Article  PubMed  CAS  Google Scholar 

  59. Cutolo M, Plebani M, Shoenfeld Y, Adorini L, Tincani A (2011) Vitamin D endocrine system and the immune response in rheumatic diseases. Vitam Horm 86:327–351

    Article  PubMed  CAS  Google Scholar 

  60. Sellitto M, Bai G, Serena G, Fricke WF, Sturgeon C, Gajer P et al (2012) Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS One 7:e33387

    Article  PubMed  CAS  Google Scholar 

  61. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D et al (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286

    Article  PubMed  CAS  Google Scholar 

  62. Macia L, Thorburn AN, Binge LC, Marino E, Rogers KE, Maslowski KM et al (2012) Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol Rev 245:164–176

    Article  PubMed  CAS  Google Scholar 

  63. Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA (2012) miRNAs and related polymorphisms in rheumatoid arthritis susceptibility. Autoimmun Rev. doi:10.1016/j.autrev.2011.11.004

  64. Kapsogeorgou EK, Gourzi VC, Manoussakis MN, Moutsopoulos HM, Tzioufas AG (2011) Cellular microRNAs (miRNAs) and Sjogren’s syndrome: candidate regulators of autoimmune response and autoantigen expression. J Autoimmun 37:129–135

    Article  PubMed  CAS  Google Scholar 

  65. Scrivo R, Vasile M, Bartosiewicz I, Valesini G (2011) Inflammation as “common soil” of the multifactorial diseases. Autoimmun Rev 10:369–374

    Article  PubMed  Google Scholar 

  66. Thamilarasan M, Koczan D, Hecker M, Paap B, Zettl UK (2012) MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun Rev 11:174–179

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA

    Carlo Selmi

  2. Clinical Immunology Unit, Department of Medicine, IRCCS Istituto Clinico Humanitas, via A. Manzoni 56, 20089, Rozzano, Milan, Italy

    Carlo Selmi

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Correspondence to Carlo Selmi.

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Selmi, C. Cutting-edge Issues in Autoimmunity and Allergy of the Digestive System. Clinic Rev Allerg Immunol 42, 265–268 (2012). https://doi.org/10.1007/s12016-012-8311-5

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