A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration

• Published in: Cellular immunology Vol. 293; no. 2; pp. 74 - 79
• Main Authors: Ashraf, Jalaluddin M., Arfat, Mir Yasir, Arif, Zarina, Ahmad, Jamal, Moinuddin, Alam, Khursheed
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-02-2015
• Subjects: Adult; Aged; Atherosclerosis - immunology; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers - blood; CEdG; Diabetes Mellitus, Type 2 - immunology; Diabetic Nephropathies - immunology; Diabetic Retinopathy - immunology; DNA; DNA - immunology; DNA - ultrastructure; Electrophoretic Mobility Shift Assay; Female; Glucose; Glycation; Glycation End Products, Advanced - immunology; Humans; Male; Nucleic Acid Conformation; Spectrophotometry, Ultraviolet; Type 2 diabetes; Type 2 diabetes; CEdG; Autoantibodies; Glucose; DNA; Glycation
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2014.12.007

•DNA-AGEs are rapidly formed with glucose. Deoxyguanosine is the epicentre of the reaction.•Unlike native DNA (B-conformation), DNA-AGE is immunologically active.•Autoantibodies against DNA-AGE formed in T2DM patients’ showed increasing trend with disease duration.•The autoantibodies appear to be involved (directly or indirectly) in secondary complications of T2DM.
Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28days at 37°C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC–MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients’ sera with disease duration of 5–15years exhibited significantly high binding with DNA-AGE as compared to patients with 1–5years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients.