Evaluation of Natural Regulatory T Cells in Subjects with Selective IgA Deficiency: From Senior Idea to Novel Opportunities

Abstract

<b><i>Background:</i></b> 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<sup>high</sup>forkhead box P3 (FoxP3)+ regulatory T cells (T<sub>reg</sub>) have been shown in association with autoimmune and inflammatory disorders. <b><i>Methods:</i></b> In order to evaluate the relationship between autoimmunity and T<sub>reg</sub> 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<sub>reg</sub> were determined by flow cytometry using T<sub>reg</sub> markers, including CD4, CD25 and FoxP3. <b><i>Results:</i></b> The mean percentage of CD4, CD25+FoxP3+ T<sub>reg</sub> 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<sub>reg</sub>, 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<sub>reg</sub> in clinical SIgAD manifestation, we classified patients into two groups: 16 patients in G1 with T<sub>reg</sub> <2.36% and 10 patients in G2 with T<sub>reg</sub> >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). <b><i>Conclusion:</i></b> This study showed decreased proportions of T<sub>reg</sub> in SIgAD patients, particularly in those with signs of chronic inflammation.