Open Access

ORIGINAL ARTICLE

Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine

Laleh Sharifi^1,2, Asghar Aghamohammadi^1,3, Nima Rezaei^3,4,5, Reza Yazdani¹, Farhad Rezaei⁶, Saied Bokaie⁷, Farzaneh Tofighi Zavareh^2,8, Fatemeh Kiaee³, Ali N. Kamali⁹, Gholamreza Azizi¹⁰, Abbas Mirshafiey^1,8

1 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
2 Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
4 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK
6 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
7 Department of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
8 Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
9 CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran
10 Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

* Corresponding Author: A. Mirshafiey, mirshafi

European Cytokine Network 2019, 30(4), 123-129. https://doi.org/10.1684/ecn.2019.0435

Accepted 06 October 2019;

Abstract

Introduction: Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination. Method: Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine. Results: Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21^low expressing B cells were found. Conclusion: Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21^low expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.

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