Background: Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25^highforkhead box P3 (FoxP3)+ regulatory T cells (T_reg) have been shown in association with autoimmune and inflammatory disorders. Methods: In order to evaluate the relationship between autoimmunity and T_reg in SIgAD, we studied 26 IgA-deficient patients (aged 4–17 years) with serum IgA levels <7 mg/dl, 26 age- and sex-matched healthy controls and 26 age- and sex matched idiopathic thrombocytopenic purpura cases with normal immune system. T_reg were determined by flow cytometry using T_reg markers, including CD4, CD25 and FoxP3. Results: The mean percentage of CD4, CD25+FoxP3+ T_reg from all CD4+ cells was 4.08 ± 0.86 in healthy controls, which was significantly higher than in SIgAD patients (2.93 ± 1.3; p = 0.003). We set a cutoff point (2.36%) for T_reg, which was two standard deviations lower than the mean of normal controls. According to this cutoff point and in order to assess the role of T_reg in clinical SIgAD manifestation, we classified patients into two groups: 16 patients in G1 with T_reg <2.36% and 10 patients in G2 with T_reg >2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). Conclusion: This study showed decreased proportions of T_reg in SIgAD patients, particularly in those with signs of chronic inflammation.

Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. Associations between poor prognosis and clinical and some immunological characteristics of the patients may help physicians to select poor prognoses patients at higher risk of mortality to develop prevention strategies for them.

Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.