Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease
| Autor: | Nima Rezaei, Fahimeh Jafarnezhad-Ansariha, Seyed Shahabeddin Mortazavi-Jahromi, Abbas Mirshafiey, Mohammadreza Shaghaghi, Reza Yazdani, Farshid Noorbakhsh, Hassan Abolhassani, Gholamreza Azizi, Asghar Aghamohammadi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent Regulatory T cell T cell Immunology Lymphocyte Activation medicine.disease_cause T-Lymphocytes Regulatory Autoimmunity Young Adult 03 medical and health sciences T-Lymphocyte Subsets RAR-related orphan receptor gamma Humans Immunology and Allergy Medicine Child Cells Cultured Exome sequencing business.industry Common variable immunodeficiency T-Lymphocytes Helper-Inducer Nuclear Receptor Subfamily 1 Group F Member 3 Flow Cytometry Milk Proteins medicine.disease Interleukin 10 Common Variable Immunodeficiency 030104 developmental biology medicine.anatomical_structure Blood Circulation Primary immunodeficiency Cytokines Female business |
| Zdroj: | Journal of Investigational Allergology and Clinical Immunology. 28:172-181 |
| ISSN: | 1018-9068 |
| DOI: | 10.18176/jiaci.0231 |
| Popis: | Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). It is characterized by heterogeneous clinical manifestations and defects in B cells and T cells. In the present study, we investigated helper T (TH) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in CVID patients with no definitive genetic diagnosis. Methods: The study population comprised 13 CVID patients and 13 healthy controls. Mutation analysis was performed using whole exome sequencing in CVID patients to rule out monogenic PIDs. TH subsets and Treg were analyzed using flow cytometry. The expression of determinant cytokines (IFN-I³, IL-17, IL-22, and IL-10) and cell subset specific transcription factors was evaluated before and after stimulation. Results: The main clinical presentations of these patients were infections only and lymphoproliferative phenotypes. No autoimmune or allergy phenotypes were recorded. The frequencies of CD4+ T cells, TH17, and Treg cells were significantly reduced in CVID patients; however, TH1, TH1-like TH17, and TH22 subsets were normal. After stimulation, expression of retinoic-acid-orphan-receptor-C (RORC), runt-related transcription factor 1 (RUNX1), IL17, and IL10 was significantly lower in CVID patients than in the healthy controls. Moreover, the concentration of IL-17 and IL-10 in the cell culture supernatants of stimulated CD4+ T cells was lower in CVID patients than in healthy controls. Conclusions: Our findings demonstrate that the imbalance of TH17 and Tregs could be associated with infection and the lymphoproliferative phenotype in CVID patients without monogenic disorders. © 2018 Esmon Publicidad. |
| Databáze: | OpenAIRE |
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