Tags

Type your tag names separated by a space and hit enter

Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease.
J Investig Allergol Clin Immunol 2018; 28(3):172-181JI

Abstract

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-γ, 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), runtrelated 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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29345621

Citation

Azizi, G, et al. "Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease." Journal of Investigational Allergology & Clinical Immunology, vol. 28, no. 3, 2018, pp. 172-181.
Azizi G, Mirshafiey A, Abolhassani H, et al. Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease. J Investig Allergol Clin Immunol. 2018;28(3):172-181.
Azizi, G., Mirshafiey, A., Abolhassani, H., Yazdani, R., Jafarnezhad-Ansariha, F., Shaghaghi, M., ... Aghamohammadi, A. (2018). Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease. Journal of Investigational Allergology & Clinical Immunology, 28(3), pp. 172-181. doi:10.18176/jiaci.0231.
Azizi G, et al. Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease. J Investig Allergol Clin Immunol. 2018;28(3):172-181. PubMed PMID: 29345621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common Variable Immunodeficiency Without Known Monogenic Disease. AU - Azizi,G, AU - Mirshafiey,A, AU - Abolhassani,H, AU - Yazdani,R, AU - Jafarnezhad-Ansariha,F, AU - Shaghaghi,M, AU - Mortazavi-Jahromi,S S, AU - Noorbakhsh,F, AU - Rezaei,N, AU - Aghamohammadi,A, Y1 - 2018/01/18/ PY - 2018/1/19/pubmed PY - 2019/9/13/medline PY - 2018/1/19/entrez KW - Autoimmunity KW - CVID KW - Common variable immunodeficiency KW - Helper T cell KW - Infection KW - Lymphoproliferative disorder KW - Regulatory T cell SP - 172 EP - 181 JF - Journal of investigational allergology & clinical immunology JO - J Investig Allergol Clin Immunol VL - 28 IS - 3 N2 - 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-γ, 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), runtrelated 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. SN - 1018-9068 UR - https://www.unboundmedicine.com/medline/citation/29345621/Circulating_Helper_T_Cell_Subsets_and_Regulatory_T_Cells_in_Patients_With_Common_Variable_Immunodeficiency_Without_Known_Monogenic_Disease_ L2 - http://www.jiaci.org/summary/vol28-issue3-num1607 DB - PRIME DP - Unbound Medicine ER -