Open Access

ORIGINAL ARTICLE

Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency

Yasser Bagheri^1,2,#, Mohsen Saeidi^1,2,#, Reza Yazdani^3,4, Fateme Babaha³, Reza Falak^5,6, Gholamreza Azizi⁷, Marjan Taherian^5,6, Fereshteh Salami³, Yaghoob Yazdani^1,2, Somayeh Sadani⁸, Ali Hosseini⁸, Morteza Motallebnezhad^5,6, Hassan Abolhassani^3,9, Mehdi Shekarabi^5,6, Asghar Aghamohammadi³

1 Stem cell research center, Golestan university of medical sciences, Gorgan, Iran
2 Immunology department, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
3 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
5 Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran
6 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
7 Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
8 Clinical Research Development Unit (CRDU), Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran
9 Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden

* Corresponding Authors:Asghar Aghamohammad, Mehdi Shekarabi, , m_ ,

European Cytokine Network 2022, 33(1), 1-12. https://doi.org/10.1684/ecn.2021.0464

Accepted 06 May 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 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.

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