Gökhan AYTEKİN, Eray YILDIZ, Osman YAŞKIRAN, Esra YAŞKIRAN, Şeyma ÇELİKBİLEK ÇELİK, Fatih ÇÖLKESEN, Sevgi KELEŞ, Recep TUNÇ

Relationship between T regulatory cell levels (CD4 + CD25 + CD127- T cells) and the presence of autoantibodies in adult patients with selective IgA deficiency

Aim: Selective immunoglobulin A (sIgA) deficiency is the most common primary immunodeficiency. Individuals with selective IgAdeficiency are generally considered to be asymptomatic. In some patients, autoimmune diseases have been reported. Regulatory Tcells (T reg) are a group of cells that play a key role in preventing autoimmunity.Material and Methods: 28 patients with selective IgA deficiency and a control group consisting of 15 individuals of similar age andsex were included in the study.Results: Serum IgA levels were lower in patients with sIgA deficiency (p < 0.001). There was no difference between the two groups interm of the rate of Treg cells (p: 0.562 and p: 0.873). There was at least one autoantibody positivity in 19 (67.8%) patients with sIgAdeficiency and 4 (26.7%) in the control group. The most common positive autoantibody was ANA in both groups. Serum IgG andIgG1 levels were significantly higher in sIgA deficiency patients with autoantibody than in the other group (p: 0.004 and p: 0.004) Therelationship between presence of autoantibodies and Treg cell levels in patients with sIgA deficiency was not statistically significant(p: 0.199). The regression analysis showed that the IgG level (OR: 1.594, 95% CI: 1.096-2.319, p: 0.015) was an independent predictorfor the presence of autoantibodies.Conclusion: The findings of our study are important as they are the first evaluation in adult sIgA deficient patients. Further studiesare required to shed light on this issue in order to evaluate more patients with sIgA deficiency with autoimmunity

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1. Yel L. Selective IgA deficiency. J Clin Immunol 2010;30:10-6.
2. Chipps BE, Talamo RC, Winkelstein JA. IgA deficiency, recurrent pneumonias, and bronchiectasis. Chest 1978;73:519-26.
3. Wang N, Shen N, Vyse TJ, et al. Selective IgA deficiency in autoimmune diseases. Molecular ed 2011;17:1383- 96.
4. Istrate C, Hinkula J, Hammarstrom L, et al. Individuals with selective IgA deficiency resolve rotavirus disease and develop higher antibody titers (IgG, IgG1) than IgA competent individuals. J Med Virol 2008;80:531-5.
5. Agarwal S, Mayer L. Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. J Allergy Clin Immunol 2009;124:658-64.
6. Janzi M, Kull I, Sjoberg R, et al. Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. Clinical immunology 2009;133:78-85.
7. Horn J, Thon V, Bartonkova D, et al. Anti-IgA antibodies in common variable immunodeficiency (CVID): diagnostic workup and therapeutic strategy. Clin Immunol 2007;122:156-62.
8. Pelkonen P, Savilahti E, Makela AL. Persistent and transient IgA deficiency in juvenile rheumatoid arthritis. Scand J Rheumatol 1983;12:273-9.
9. Rankin EC, Isenberg DA. IgA deficiency and SLE: prevalence in a clinic population and a review of the literature. Lupus 1997;6:390-4.
10. Badcock LJ, Clarke S, Jones PW, Dawes PT, Mattey DL. Abnormal IgA levels in patients with rheumatoid arthritis. Ann Rheum Dis 2003;62:83-4.
11. McGowan KE, Lyon ME, Butzner JD. Celiac disease and IgA deficiency: complications of serological testing approaches encountered in the clinic. Clin Chem 2008;54:1203-9.
12. Ramanujam R, Piehl F, Pirskanen R, et al. Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency. J Neuroimmunol 2011;236:118-22.
13. Kurien M, Leeds JS, Hopper AD, et al. Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary? Diabet Med 2013;30:840-5.
14. Barka N, Shen GQ, Shoenfeld Y, et al. Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. Clinical and diagnostic laboratory immunology. 1995;2:469- 72.
15. Gulez N, Karaca NE, Aksu G, et al. Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations. Autoimmunity 2009;42:74-9.
16. Campbell DJ. Control of Regulatory T Cell Migration, Function, and Homeostasis. J Immunology 2015;195:2507-13.
17. Mills KH. Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 2004;4:841-55.
18. Belizario JE, Brandao W, Rossato C, et al. Thymic and Postthymic Regulation of Naive CD4(+) T-Cell Lineage Fates in Humans and Mice Models. Mediators of Inflammation 2016;2016:9523628.
19. Soheili H, Abolhassani H, Arandi N, et al. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities. Int Arch Allergy Immuno 2013;160:208-14.
20. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical ımmunology 1999;93:190-7.
21. Yu N, Li X, Song W, et al. CD4(+)CD25 (+)CD127 (low/- ) T cells: a more specific Treg population in human peripheral blood. Inflammation 2012;35:1773-80.
22. Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, et al. Clinical symptoms in adults with selective IgA deficiency: a case-control study. J Clin Immunol 2013;33:742-7.
23. Etzioni A. Immune deficiency and autoimmunity. Autoimmun Rev 2003;2:364-9.
24. Miller FW, Pollard KM, Parks CG, et al. Criteria for environmentally associated autoimmune diseases. J Autoimmun 2012;39:253-8.
25. Zhang H, Li P, Wu D, Xu D, Hou Y, Wang Q, et al. Serum IgG subclasses in autoimmune diseases. Medicine 2015;94:387.
26. Liu H, May K. Disulfide bond structures of IgG molecules: structural variations, chemical modifications and possible impacts to stability and biological function. mAbs 2012;4:17-23.
27. Takahashi H, Yamamoto M, Suzuki C, et al. The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. Autoimmun Rev 2010;9:591-4.
28. Moschese V, Graziani S, Avanzini MA, Carsetti R, Marconi M, La Rocca M, et al. A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network. Int J Immunopathol Pharmacol 2008;21:343-52.
29. Lin GG, Li JM. IgG subclass serum levels in systemic lupus erythematosus patients. Clin Rheumatol 2009;28:1315-8.
30. Satoh M, Chan EK, Ho LA, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis and rheumatism. 2012;64:2319-27.