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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

T Cell Proliferative Responses and IgG Antibodies to β2GPI in Patients with Diabetes and Atherosclerosis

Author(s): Mohammad R. Monjezi, Hamed Fouladseresht, Shirin Farjadian, Behrouz Gharesi-Fard, Shahdad Khosropanah and Mehrnoosh Doroudchi*

Volume 21 , Issue 3 , 2021

Published on: 05 May, 2020

Page: [495 - 503] Pages: 9

DOI: 10.2174/1871530320666200505115850

Price: $65

Abstract

Background: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. Tlymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (β2GPI) are shown in carotid atherosclerosis.

Objective: To investigate the self-reactive, β2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis.

Methods: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Non-diabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: AD- (n=31). All groups were evaluated for anti-β2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with β2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles.

Results: Mean β2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02). The co-presence of diabetes in A+ individuals increased mean β2GPI-specific IgG. Auto-reactive β2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. β2GPI-peptides showed promiscuous restriction by various HLADRB1.

Conclusion: β2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of β2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help the development of immunomodulation methods to prevent or treat these debilitating diseases.

Keywords: Diabetes mellitus, atherosclerosis, CFSE dilution assay, HLA-DRB1, immunoglobulin G, beta 2-Glycoprotein I.

Graphical Abstract
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