TY  - EJOU
AU  - Bagheri, Yasser 
AU  - Saeidi, Mohsen 
AU  - Yazdani, Reza 
AU  - Babaha, Fateme 
AU  - Falak, Reza 
AU  - Azizi, Gholamreza 
AU  - Taherian, Marjan 
AU  - Salami, Fereshteh 
AU  - Yazdani, Yaghoob 
AU  - Sadani, Somayeh 
AU  - Hosseini, Ali 
AU  - Motallebnezhad, Morteza 
AU  - Abolhassani, Hassan 
AU  - Shekarabi, Mehdi 
AU  - Aghamohammadi, Asghar 

TI  - Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency
T2  - European Cytokine Network

PY  - 2022
VL  - 33
IS  - 1
SN  - 1952-4005

AB  - 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.
KW  - selective IgA deficiency
KW  -  B cell
KW  -  IL-10
KW  -  STAT3
KW  -  TGF-b
KW  -  apoptosis

DO  - 10.1684/ecn.2021.0464