Evaluation of Effective Factors on Il-10 Signaling in B Cells in Patients With Selective Iga Deficiency Publisher Pubmed



Bagheri Y^{1, 2} ; Saeidi M^{1, 2} ; Yazdani R^{3, 4} ; Babaha F³ ; Falak R^{5, 6} ; Azizi G⁷ ; Taherian M^{5, 6} ; Salami F³ ; Yazdani Y^{1, 2} ; Sadani S⁸ ; Hosseini A⁸ ; Motallebnezhad M^{5, 6} ; Abolhassani H^{3, 9} ; Shekarabi M^{5, 6} Show All Authors Show Affiliations
Source: European Cytokine Network Published:2021

Abstract

Background: Selective IgA deficiency is the most prevalent form of primary immunodeficiencies. The pathogenesis of the disease is still unknown. Several studies have suggested a defect in B cell responses to IL-10; however, the main reason for this defect has not been reported. Elucidating IL-10 signaling defects and their correlation with clinical manifestations could be helpful for better understanding and treatment of the disease. Methods: In this study, 15 SIgAD patients and 15 age- and sex-matched healthy controls were included. Surface expression of transforming growth factor β receptor II (TGF-β RII), IL-10R and IgA was assessed by flow cytometry in human purified B cells before and after stimulation by IL-10. Protein expression of STAT3, p-STAT3 and SOCS3 was measured by Western blotting analysis. TGF-β and IgA secretion was evaluated by ELISA. Finally, the measurement of B cell apoptosis was performed by flow cytometry. Results: The TGF-βRII expression level was decreased after stimulation with IL-10 in patients compared with controls. Notably, the TGF-β level were higher after stimulation with mCD40L and IL-10 in the control group as compared to stimulation with mCD40L alone. The IgA+ B cell percentage and IgA secretion levels were significantly increased in controls as compared with SIgAD patients. The relative concentration of the total STAT3 was decreased as compared with controls. Conclusion: The defect in IgA production in SIgAD patients could be due to inadequate B cell responses to IL-10 stimulation that probably originate from defective regulation of IL-10-mediated TGF-b ‘symbol’ production TGF-β response by IL-10. Furthermore, it is suggested that the absence of STAT3 protein baseline expression could impair cytokine-mediated signaling such as thatinduced by IL-!0 and IL-21. © 2021, JLE/Springer.