Mohd Yasir Khan1, Sultan Alouffi2, Mohd Shahnawaz Khan3, Fohad Mabood Husain3, Firoz Akhter4, Saheem Ahmad5. 1. IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India. 2. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia. 3. Protein Research Chair, Department of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia; Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11541, Saudi Arabia. 4. Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA. 5. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia. Electronic address: s.ansari@uoh.edu.sa.
Abstract
AIMS: Non-enzymatic reaction of biomolecules leads to the formation of advanced glycation end products (AGEs). AGEs plays significant role in the pathophysiology of type 2 diabetes mellitus. Methylglyoxal (MG) is a highly reactive carbonyl compound which causes formation of early (ketoamines), intermediate (dicarbonyls) and advanced glycation end products (AGEs). Glycation also results in the generation of free radicals causing structural perturbations which leads to the generation of neoantigenic epitopes on LDL molecules. The aim of the present study was to investigate whether the modification of LDL results in auto-antibodies generation in type 2 diabetes patients'. METHODS: The binding affinity of circulating autoantibodies in patients against native and MG modified LDL were assessed as compared with healthy and age-matched controls (n = 50) and T2DM patients with disease duration (DD) 5-15 yrs (n = 80) and DD > 15 yrs (n = 50) were examined by direct binding ELISA. KEY FINDINGS: The high affinity binding were observed in 50% of T2DM with DD 5-15 and 62% of T2DM with DD > 15 of patient's sera antibodies to MG-LDL antigen, in comparison to its native analog (P < 0.05). NHS sera showed negligible binding with both native and glycated LDL. Competitive inhibition ELISA results exhibit greater affinity sera IgG than the direct binding ELISA results. The increase in glycation intermediate and ends product were also observed in T2DM patient's sera and NHS sera. SIGNIFICANCE: There might be the generation of neoantigenic epitopes on LDL macromoleucle which results in generation of antibodies in T2DM. The prevalence of antibodies was dependent on disease duration.
AIMS: Non-enzymatic reaction of biomolecules leads to the formation of advanced glycation end products (AGEs). AGEs plays significant role in the pathophysiology of type 2 diabetes mellitus. Methylglyoxal (MG) is a highly reactive carbonyl compound which causes formation of early (ketoamines), intermediate (dicarbonyls) and advanced glycation end products (AGEs). Glycation also results in the generation of free radicals causing structural perturbations which leads to the generation of neoantigenic epitopes on LDL molecules. The aim of the present study was to investigate whether the modification of LDL results in auto-antibodies generation in type 2 diabetespatients'. METHODS: The binding affinity of circulating autoantibodies in patients against native and MG modified LDL were assessed as compared with healthy and age-matched controls (n = 50) and T2DM patients with disease duration (DD) 5-15 yrs (n = 80) and DD > 15 yrs (n = 50) were examined by direct binding ELISA. KEY FINDINGS: The high affinity binding were observed in 50% of T2DM with DD 5-15 and 62% of T2DM with DD > 15 of patient's sera antibodies to MG-LDL antigen, in comparison to its native analog (P < 0.05). NHS sera showed negligible binding with both native and glycated LDL. Competitive inhibition ELISA results exhibit greater affinity sera IgG than the direct binding ELISA results. The increase in glycation intermediate and ends product were also observed in T2DM patient's sera and NHS sera. SIGNIFICANCE: There might be the generation of neoantigenic epitopes on LDL macromoleucle which results in generation of antibodies in T2DM. The prevalence of antibodies was dependent on disease duration.
Authors: Hamda Khan; Mohd Waseem; Mohammad Faisal; Abdulrahman A Alatar; Ahmed A Qahtan; Saheem Ahmad Journal: Biomed Res Int Date: 2021-04-09 Impact factor: 3.411
Authors: Saheem Ahmad; Sultan Alouffi; Saif Khan; Mahvish Khan; Rihab Akasha; Jalaluddin Mohammad Ashraf; Mohd Farhan; Uzma Shahab; Mohd Yasir Khan Journal: Biomed Res Int Date: 2022-01-19 Impact factor: 3.411