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The circulating T helper subsets and regulatory T cells in patients with common variable immunodeficiency with no known monogenic disease

Azizi G1,2,3, Mirshafiey A2,4*, Abolhassani H2,3,5, Yazdani R2, Ansariha FJ4, Shaghaghi M2,6, Mortazavi-Jahromi SS4, Noorbakhsh F7, Rezaei N2,6,7, Aghamohammadi A2,3*

1Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
2Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
3Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
4Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
5Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
6Network of Immunology in Infections, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
7Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

J Investig Allergol Clin Immunol 2018; Vol. 28(3)
doi: 10.18176/jiaci.0231

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis.
Methods: The study population comprised 13 CVID patients and 13 healthy controls (HC). Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (IFN-γ, IL-17, IL-22, and IL-10), and cell subset specific transcription factors were evaluated before and after stimulation.
Results: The main clinical presentations of these patients were infections only and lymphoproliferations phenotypes, but no autoimmune and allergy phenotype were recorded. The frequencies of CD4+ T cells, Th17, and Treg cells were significantly reduced in CVID patients, however the subsets of Th1, Th1-like Th17 and Th22 cells were normal. After stimulation, retinoic-acid-orphan-receptor-C (RORC), and runt-related transcription factor 1 (RUNX1), IL17, and IL10 genes’ expression in CVID patients were significantly lower, in comparison to the HC. Moreover, there was a lower concentration of IL-17 and IL-10 in cell culture supernatants of stimulated CD4+ T cells of CVID patients than HC.
Conclusions: Our findings demonstrate that the imbalance of Th17 and Tregs could be an associated with infections only and lymphoproliferations phenotype in CVID patients without monogenic disorders.

Key words: Common variable immunodeficiency, CVID, Infection, Autoimmunity, Lymphoproliferations, Regulatory T cell, T helper cell

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