Title:T Cell Proliferative Responses and IgG Antibodies to β2GPI in Patients with Diabetes and Atherosclerosis
Volume: 21
Issue: 3
Author(s): Mohammad R. Monjezi, Hamed Fouladseresht, Shirin Farjadian, Behrouz Gharesi-Fard, Shahdad Khosropanah and Mehrnoosh Doroudchi*
Affiliation:
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz,Iran
Keywords:
Diabetes mellitus, atherosclerosis, CFSE dilution assay, HLA-DRB1, immunoglobulin G, beta 2-Glycoprotein I.
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.
