Nonenzymatic glycosylation of human serum albumin and its effect on antibodies profile in patients with diabetes mellitus
| العنوان: | Nonenzymatic glycosylation of human serum albumin and its effect on antibodies profile in patients with diabetes mellitus |
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| المؤلفون: | Khursheed Alam, Alok Raghav, Jamal Ahmad |
| المصدر: | PLoS ONE, Vol 12, Iss 5, p e0176970 (2017) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Glycation End Products, Advanced, 0301 basic medicine, Physiology, lcsh:Medicine, Antigen-Antibody Complex, Immune Complex, Biochemistry, Immunoglobulin G, Epitopes, chemistry.chemical_compound, Endocrinology, Spectrum Analysis Techniques, 0302 clinical medicine, Glycation, Immune Physiology, Spectroscopy, Fourier Transform Infrared, Medicine and Health Sciences, Glycated Serum Albumin, Enzyme-Linked Immunoassays, Post-Translational Modification, lcsh:Science, Immune System Proteins, Multidisciplinary, biology, Organic Compounds, Monosaccharides, Absorption Spectroscopy, Middle Aged, Human serum albumin, Gestational diabetes, Chemistry, 030220 oncology & carcinogenesis, Physical Sciences, Female, Rabbits, Research Article, medicine.drug, Adult, medicine.medical_specialty, Glycosylation, Adolescent, Endocrine Disorders, Immunology, Carbohydrates, Serum albumin, Enzyme-Linked Immunosorbent Assay, Research and Analysis Methods, Antibodies, Young Adult, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Animals, Humans, Antigens, Immunoassays, Serum Albumin, Aged, Organic Chemistry, lcsh:R, Chemical Compounds, Albumin, Biology and Life Sciences, Proteins, medicine.disease, Glucose, Diabetes Mellitus, Type 1, 030104 developmental biology, Diabetes Mellitus, Type 2, chemistry, Immune System, Metabolic Disorders, Immunologic Techniques, biology.protein, lcsh:Q, Blood Chemical Analysis, Chromatography, Liquid |
| الوصف: | Background Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. Methods Human Serum Albumin (HSA) was modified with D-glucose for a 40 day period under sterile conditions at 37EC. Modified samples along with native HSA (unmodified) were analyzed for structural modifications by UV and fluorescence, FTIR, Liquid chromatography mass spectrometry (LCMS) and X±ray crystallography. New-Zealand white female rabbits immunized with AGEs, represent auto-Antibodies formation as assessed by competitive and direct binding enzyme-linked immunosorbent assay (ELISA). Neo-epitopesagainst In-vitro formed AGEs were characterized in patients with diabetes mellitus type 2 (n = 50), type 1 (n = 50), gestational diabetes (n = 50) and type 2 with chronic kidney disease (CKD) with EGFR level 60±89 mL/min (n = 50) from serum direct binding ELISA. Results Glycated-HSA showed amarked increase in hyperchromicity of 65.82%,71.98%, 73.62% and 76.63% at γ280 nm along with anincreasein fluorescence intensity of 65.82%, 71.98%, 73.62% and 76.63% in glycated-HSA compared to native. FTIR results showed theshifting of Amide I peak from 1656 cm-1 to 1659 cm-1 and Amide II peak from 1554 cm-1 to 1564 cm-1 in glycated-HSA, with anew peak appearance of carbonyl group at 1737 cm-1. LCMS chromatogram of glycated-HSA showed thepresence of carboxymethyl lysine (CML) at 279.1 m/z. Immunological analysis showed high antibody titre>1:12,800 in theserum of rabbits immunized with glycated-HSA (modified with 400 mg/dL glucose) and inhibition of 84.65% at anantigen concentration of 20μg/mL. Maximum serum auto-Antibody titre was found in T2DM (0.517±0.086), T1DM (0.108±0.092), GDM (0.611±0.041) and T2DM +CKD (0.096±0.25) patients immunized with glycated-HSA (modified with 400 mg/dL glucose). Conclusions Non-enzymatic glycosylation of HSA manifests immunological complications in diabetes mellitus due to change in its structure that enhances neo-epitopes generation. © 2017 Grelet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8842f2b354a6bfcab188d246f1e0237Test http://europepmc.org/articles/PMC5435419?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a8842f2b354a6bfcab188d246f1e0237 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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