Stem cell research center, Golestan university of medical sciences, Gorgan, Iran
Immunology department, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Clinical Research Development Unit (CRDU), Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
Correspondence: Asghar Aghamohammadi, Children’s Medical Center Hospital, 62 Qarib St., Keshavarz Blvd., Tehran 14194, Iran.
Mehdi Shekarabi, Department of Immunology, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran: M. Shekarabi
a These authors contributed equally to this article.
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.
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.
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.
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.