Circulating antibodies against age-modified proteins in patients with coronary atherosclerosis

Abstract

Advanced glycation endproducts (AGEs) are formed in a series of non-enzymatic reactions between reducing sugars and the amino groups of proteins and accumulate during aging, diabetes mellitus, chronic kidney disease and other chronic diseases. Accumulation of AGE-modifications alters protein structure and function, transforming these molecules into potential targets of the immune system, presumably triggering the production of autoantibodies against AGEs. In this study, we detected autoantibodies against AGE-modified proteins with ELISA in plasma samples of 91 patients with documented coronary artery disease (CAD), who underwent coronary artery bypass grafting (CABG) surgery. Patients with high levels of autoantibodies had a higher body mass index (BMI 28.6 vs 27.1 kg/m2; p = 0.046), were more likely to suffer from chronic obstructive pulmonary disease (COPD 30% vs 9.8%; p = 0.018), and more likely to need dialysis after the surgery (10% vs 0%; p = 0.037). Our findings show a weak link between the levels of autoantibodies against AGEs and diabetes mellitus (DM 44% vs 24.4%; p = 0.05). In a small subpopulation of patients, antibodies against native bovine serum albumin (BSA) were detected. A growing body of research explores the potential role of antibodies against AGE-modified proteins in pathogenesis of different chronic diseases; our data confirms the presence of AGE-autoantibodies in patients with CAD and that in parallel to the AGEs themselves, they may have a potential role in concomitant clinical conditions in patients undergoing CABG surgery. Further research is necessary to verify the molecular role of these antibodies in different pathological conditions.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

“…The accumulation of AGEs changes the structure and function of proteins, turning them into potential targets of the immune system, which can result in the production of autoantibodies against AGEs. Albumin was no exception; HSA antibodies were found in the blood of patients with atherosclerotic vascular injury and signs of DM [ 161 ]. Moreover, IgG and IgA autoantibodies to HSA may have diagnostic value in autoimmune bullous dermatoses (ABD), while cutaneous autoantigens have not yet been identified [ 162 ].…”

Proteins in human body fluids contain in vivo antigen analog of the melibiose-derived glycation product: MAGE

“…Significance of our study refers to the glycation-induced change in function of the circulating natural antibodies and potentially some therapeutic antibodies used recently more often in clinics. AGEs increase immunogenicity of immunoglobulins and cause production of antibodies against this modified protein 77 , as reported in type 2 diabetes 78 , atherosclerosis 79 , and rheumatoid arthritis (RA) 80 – 82 . Glycation is also a suspected cause of decreased elimination of IgA by the liver and the protein accumulation in blood 83 .…”

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression

“…The exact role of anti-AGE antibodies in the pathophysiology of diabetes is not fully understood. It is thought that they may be part of a defense mechanism that serves to remove damaged or dysfunctional proteins as a result of enhanced AGE modifications [ 48 ]. In this regard, the likely role of anti-AGE EL IgM and anti-AGE EL IgG antibodies is that they may be involved in the removal of damaged glycated vascular EL and its metabolites through the formation of circulating immune complexes and their subsequent elimination by a mononuclear phagocytic system.…”