Evaluation of immunophenotype in patients with selective immunoglobulin a deficiency with and without autoimmune and/or inflammatory diseases compared to a healthy control group.

Selective Immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency (PID) characterized by low serum immunoglobulin (Ig) A levels and normal IgG and IgM levels. Autoimmune diseases are among the most important clinical manifestations of IgA deficiency. Toll-like receptors (TLRs) play an important role in initiating innate and adaptive immune responses, and the pattern-recognizing receptors TLR- 7 and TLR-9 are responsible for recognizing nucleic acids produced by viruses, bacteria, and necrotic cells. When cell or tissue damage occurs and B cell responses to endogenous nucleic acids cannot be limited, autoantibodies and autoimmunity may occur. This study aimed to compare TLR-7 and TLR-9 expression levels in SIgAD patients with or without autoimmune/inflammatory diseases and to investigate whether TLR-7 and TLR-9 have an effect on the development of autoimmunity. Autoimmune disease or autoantibody positivity was detected in 39 (19.1%) of 204 patients diagnosed with SIgAD. 17 patients with autoimmune/inflammatory disease and 15 patients without autoimmune/inflammatory disease were reached and included in the study. Two patient groups between the ages of 4 and 25 were compared with a group of 15 healthy individuals with similar age and gender distributions. Clinical and immunological features of the patients were examined retrospectively, and TLR-7 and TLR-9 expressions were studied prospectively in the control and patient groups using real-time quantitative polymerase chain reaction analysis. The rate of patients with autoimmune disease in the entire SIgAD cohort was 19.1%. Of the patients with autoimmune disease, seven (41.2%) had Hashimoto's thyroiditis, five (29.4%) had type 1 diabetes mellitus, five (29.4%) had celiac antibody positivity, two (11.8%) had Graves' disease, one (5.9%) had autoimmune hepatitis, one (5.9%) had juvenile idiopathic arthritis and one (5.9%) had systemic lupus erythematosus. In this study, unlike other PIDs, autoimmune endocrinopathies were more common in cases with SIgAD, not autoimmune cytopenia. Multiple autoantibody positivity was detected in five (29.4%) of the patients. IgG levels were higher in the group with accompanying autoimmune disease compared to the other two groups (p=0.011). No significant difference was found between patients with and without autoimmune disease and the control group in terms of TLR-7 and TLR-9 target gene expression levels (p>0.05). Although it was not found to be statistically significant in our study, the median TLR-7 expression levels of patients with SIgAD diagnosis accompanied by autoimmune disease were higher (2.14 vs. 1.3; 1.07). When the single or multiple autoimmunity status was compared with control group, the TLR-7 expression level of those with single autoantibody positivity were found to be statistically significantly higher (p=0.036). In the group accompanied by autoimmune disease, a high negative correlation was found between IgG (P:0.01; R:-0.604) and CD3 level (P:0.005 R:-0.642) and TLR-7 expression levels, and a moderate negative correlation was found between CD4 level (P:0.043; R:-0.495) and TLR-7 expression levels. The high IgG levels in the group accompanied by autoimmune disease compared to the other two groups may be due to the formation of autoantibodies of IgG nature in the patients. Although the TLR-7 expression levels were higher in patients diagnosed with SIgAD accompanied by autoimmune disease, it was thought that it did not reach statistical significance due to the small number of patients. It was thought that the findings related to the disease pathogenesis were more active in patients with single autoimmune disease. This study is a supportive study in terms of understanding the mechanism of autoimmunity and will guide further studies.