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

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