Methylglyoxal mediated glycation leads to neo-epitopes generation in fibrinogen: Role in the induction of adaptive immune response.

In diabetes mellitus, hyperglycemia mediated non-enzymatic glycosylation of proteins results in the pathogenesis of diabetes-associated secondary complications via the generation of advanced glycation end products (AGEs). The focus of this study is to reveal the immunological aspects of methylglyoxal (MG) mediated glycation of fibrinogen protein. The induced immunogenicity of modified fibrinogen is analyzed by direct binding and inhibition ELISA. Direct binding ELISA confirmed that MG glycated fibrinogen (MG-Fib) is highly immunogenic and induces a high titer of antibodies in comparison to its native analog. Cross-reactivity and antigen-binding specificity of induced antibodies were confirmed by inhibition ELISA. The enhanced affinity of immunoglobulin G (IgG) from immunized rabbits' sera and MG glycated fibrinogen is probably the aftermath of neo-epitopes generation in the native structure of protein upon modification. Thus, we deduce that under the glycative stress, MG-mediated structural alterations in fibrinogen could induce the generation of antibodies which might serve as a potential biomarker in diabetes mellitus and its associated secondary disorders.