T Cell Proliferative Responses And Igg Antibodies To Beta 2gpi In Patients With Diabetes And Atherosclerosis

Background: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. T-lymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (beta 2GPI) are shown in carotid atherosclerosis.Objective: To investigate the self-reactive, beta 2GPI-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: A-D- (n=31). All groups were evaluated for anti-beta 2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with beta 2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles.Results: Mean beta 2GPI 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 beta 2GPI-specific IgG. Auto-reactive beta 2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. beta 2GPI-peptides showed promiscuous restriction by various HLA-DRB1.Conclusion: beta 2GPI 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 beta 2GPI 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.