@Article{ecn.2021.0464,
AUTHOR = {Yasser Bagheri, Mohsen Saeidi, Reza Yazdani, Fateme Babaha, Reza Falak, Gholamreza Azizi, Marjan Taherian, Fereshteh Salami, Yaghoob Yazdani, Somayeh Sadani, Ali Hosseini, Morteza Motallebnezhad, Hassan Abolhassani, Mehdi Shekarabi, Asghar Aghamohammadi},
TITLE = {Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency},
JOURNAL = {European Cytokine Network},
VOLUME = {33},
YEAR = {2022},
NUMBER = {1},
PAGES = {1--12},
URL = {http://www.techscience.com/ECN/v33n1/65052},
ISSN = {1952-4005},
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 was 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-β production or 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 that induced by IL-10 and IL-21.},
DOI = {10.1684/ecn.2021.0464}
}