Preferential recognition of advanced glycation end products by serum antibodies and low-grade systemic inflammation in diabetes mellitus and its complications
Abstract
Background Advanced glycation end products (AGEs) have shown to possess antigenicity. This study analyzes the detrimental effect of non-enzymatic glycation on human serum albumin (HSA) leading to the production of antibodies. Methods HSA (20 μM) incubated with d-glucose formed AGEs confirmed by scanning electron microscopy (SEM). DNA-damage was assessed with comet assay. Antibodies against in-vitro formed AGEs was evaluated in the sera of diabetic patients by enzyme-linked immunosorbent assay. Molecular docking was performed to demonstrate affinity of native and glycated-HSA with IgG. Low-grade systemic inflammation was quantified with IL-4, IL-6, TNF-α and NF-кβ in serum and mRNA expression. Results Scanning Electron Microscopy showed the formation of aggregates in glycated-HSA. Comet assay showed DNA damage T2DM with CKD. Serum auto-antibodies in diabetes patients with chronic kidney disease (CKD) showed appreciably high recognition with glycated-HSA compared to native HSA. Molecular docking showed less affinity of glycated-HSA with IgG. Serum IL-4, IL-6, and TNF-α were found significantly higher in T2DM with CKD compared to T2DM and healthy ones. mRNA expression of IL-4, IL-6 and NF-кβ are also found significantly higher in T2DM with CKD. Conclusion The non-enzymatic glycation-induced damage to the HSA generate neo-epitopes that possess immunogenic response and low-grade systemic inflammation.
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The AP-1 factors c-Jun and JunB are critical interacting partners with PU.1 that also regulate myeloid differentiation, including PU.1 expression.
“Indeed, the AP-1 factors c-Jun and JunB are also critical interacting partners with PU.1 that also regulate myeloid differentiation (including PU.1 expression) (Steidl et al., 2006; Raghav et al., 2018; Zhao et al., 2022).”
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Cites
Avogadro: an advanced semantic chemical editor, visualization, and analysis platform
Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. (2012) · Journal of Cheminformatics · doi:10.1186/1758-2946-4-17 · Cited by 10,636 · see citing works
Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes
Fu, Z., Gilbert, E. R., & Liu, D. (2012) · Current Diabetes Reviews · doi:10.2174/157339913804143225 · Cited by 882 · see citing works
Regulation of metabolism by the innate immune system
Lackey, D. E., & Olefsky, J. M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.189 · Cited by 667 · see citing works
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.
Fu, Z., Gilbert, E. R., & Liu, D. (2013) · PubMed · Cited by 600 · see citing works
Uribarri, J., Cai, W., Peppa, M., Goodman, S., Ferrucci, L., Striker, G., & Vlassara, H. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.4.427 · Cited by 570 · see citing works
In situ production of TNF-α, IL-1β and IL-2R in ANCA-positive glomerulonephritis
Noronha, I. L., Krüger, C., Andrássy, K., Ritz, E., & Waldherr, R. (1993) · Kidney International · doi:10.1038/ki.1993.98 · Cited by 282 · see citing works
Inflammatory Cytokines in Diabetic Nephropathy
Donate‐Correa, J., Martín‐Núñez, E., Muros‐de‐Fuentes, M., Fernández, C. M., & Navarro‐González, J. F. (2015) · Journal of Diabetes Research · doi:10.1155/2015/948417 · Cited by 278 · see citing works
Ketema, E. B., & Kibret, K. T. (2015) · Archives of Public Health · doi:10.1186/s13690-015-0088-6 · Cited by 237 · see citing works
Role of inflammation in diabetic complications
Navarro‐González, J. F., & Mora, C. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfi155 · Cited by 227 · see citing works
The role of the immune system in kidney disease
Tecklenborg, J., Clayton, D., Siebert, S., & Coley, S. M. (2018) · Clinical & Experimental Immunology · doi:10.1111/cei.13119 · Cited by 220 · see citing works
Inflammation and cachexia in chronic kidney disease
Cheung, W. W., Paik, K. H., & MAK, R. H. K. (2010) · Pediatric Nephrology · doi:10.1007/s00467-009-1427-z · Cited by 162 · see citing works
Akhter, F., Khan, M. S., Alatar, A. A., Faisal, M., & Ahmad, S. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.02.013 · Cited by 49 · see citing works
Glycated serum albumin: A potential disease marker and an intermediate index of diabetes control
Raghav, A., & Ahmad, J. (2014) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2014.09.017 · Cited by 43 · see citing works
Self-citationRaghav, A., Ahmad, J., & Alam, K. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176970 · Cited by 40 · see citing works
Self-citationAcquired immunogenicity of calf thymus DNA and LDL modified by d-ribose: A comparative study
Akhter, F., Khan, M. S., & Ahmad, S. (2014) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2014.10.034 · Cited by 40 · see citing works
Studies of advanced glycation end products and oxidation biomarkers for type 2 diabetes
Chiu, C., Rabbani, N., Rowan, S., Chang, M., Sawyer, S. J., Hu, F. B., Willett, W. C., Thornalley, P. J., Anwar, A., Bar, L. K., et al. (2018) · BioFactors · doi:10.1002/biof.1423 · Cited by 38 · see citing works
Siddiqui, Z., Ishtikhar, M., Moinuddin, M., & Ahmad, S. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.01.161 · Cited by 35 · see citing works
[Correlations of insulin resistance and neoplasms].
Suba, Z., & Ujpál, M. (2006) · PubMed · Cited by 33 · see citing works
Khan, M. Y., Alouffi, S., & Ahmad, S. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.04.016 · Cited by 31 · see citing works
Biophysical and biochemical studies on glycoxidatively modified human low density lipoprotein
Abidi, M., Khan, M. S., Ahmad, S., Kausar, T., Nayeem, S. M., Islam, S., Ali, A., Alam, K., & Moinuddin, M. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.02.019 · Cited by 29 · see citing works
Self-citationRaghav, A., Ahmad, J., Alam, K., & Khan, A. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.03.086 · Cited by 26 · see citing works
Self-citationRaghav, A., Ahmad, J., & Alam, K. (2015) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2015.10.009 · Cited by 15 · see citing works
Self-citationAssiri, A. M. A., Kamel, H. F. M., & ALrefai, A. A. (2018) · Medical Sciences · doi:10.3390/medsci6020038 · Cited by 10 · see citing works
Ma, X., He, J., Yan, J., Wang, Q., & Li, H. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.02.009 · Cited by 9 · see citing works
Ansari, S. A., Jafri, M., Satar, R., Ahmad, S. I., & Chibber, S. (2018) · Oriental Journal Of Chemistry · doi:10.13005/ojc/340227 · Cited by 7 · see citing works
Amelioration of 5-FU induced toxicity by using RF under white light: An in vitro study
Larramendy, M. L., & National University of La Plata (2015) · Integrative Pharmacology Toxicology and Genotoxicology · doi:10.15761/iptg.1000108 · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 27 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Ultrasound-assisted extraction and characteristics of maize polysaccharides from different sites
Song, Z., Xiong, X., & Huang, G. (2023) · Ultrasonics Sonochemistry · doi:10.1016/j.ultsonch.2023.106416 · Cited by 81 · see citing works
Möller, P., Stopper, H., & Collins, A. R. (2019) · Mutagenesis · doi:10.1093/mutage/gez018 · Cited by 76 · see citing works
Nabrdalik-Leśniak, D., Nabrdalik, K., Sedlaczek, K., Główczyński, P., Kwiendacz, H., Sawczyn, T., Hajzler, W., Drożdż, K., Hendel, M., Irlik, K., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5593589 · Cited by 22 · see citing works
PU.1 is required to restrain myelopoiesis during chronic inflammatory stress
Chavez, J. S., Rabe, J. L., Niño, K. E., Wells, H. H., Gessner, R. L., Mills, T. S., Hernandez, G., & Pietras, E. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1204160 · Cited by 14 · see citing works
Meng, Y., He, Y., Zhang, J., Xie, Q., Yang, M., Chen, Y., & Wu, Y. (2019) · Medicine · doi:10.1097/md.0000000000016716 · Cited by 14 · see citing works
Chokeberry reduces inflammation in human preadipocytes
Brunelle, D. C., Larson, K., Bundy, A. N., Roemmich, J. N., Warne, D. K., & Redvers, N. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105947 · Cited by 8 · see citing works
Genotoxic markers in patients with diabetes mellitus (Literature review)
Eremina, N. V., Жанатаев, А. К., Lisitsyn, A. A., & Durnev, A. D. (2021) · Ecological genetics · doi:10.17816/ecogen65073 · Cited by 8 · see citing works
Advanced glycation end products impair the repair of injured tendon: a study in rats
Yang, J., He, J., & Yang, L. (2024) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-024-07760-z · Cited by 7 · see citing works
Natural Products as Wound Healing Agents
Khalil, E. A., Abouzekry, S., Sami, D. G., & Abdellatif, A. (2021) · Springer eBooks · doi:10.1007/978-981-16-2677-7_3 · Cited by 6 · see citing works
Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids
Liu, L., Liu, Y., Xiao, A., Mei, S., & Xie, Y. (2019) · Open Chemistry · doi:10.1515/chem-2019-0079 · Cited by 5 · see citing works
Jia, G., Jia, X., Yang, J., Shi, T., Qiang, M., & Chen, Y. (2024) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-024-00800-7 · Cited by 2 · see citing works
Glycated albumin as a surrogate marker for prediabetes: a cross-sectional study
Alam, S., Ahmad, F., Tripathi, P., & Raghav, A. (2023) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-023-01250-z · Cited by 1 · see citing works
Self-citationMohamadzadeh, S., Rahimian, S., Amini, B., Jafarian, V., & Mirzaee, Z. (2026) · BioNanoScience · doi:10.1007/s12668-026-02502-y · Cited by 1 · see citing works
Lapolla, A. (2021) · Mass Spectrometry Reviews · doi:10.1002/mas.21742 · Cited by 1 · see citing works
Raghav, A., Ashraf, H., & Ahmad, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1767858
Self-citation
- Authors
- Raghav, A., Ahmad, J., & Alam, K.
- Affiliations
- Aligarh Muslim University (IN)
- Corresponding author
- Ahmad, Jamal
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 118
- Issue
- Pt B
- Pages
- 1884-1891
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2883840479
- Cited by
- 15
- References
- 27
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 4 · 2021: 4 · 2019: 3
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Keywords
- advanced glycation end products, glycation, human serum albumin, autoantibodies, type 2 diabetes, chronic kidney disease, low-grade inflammation, DNA damage, neoantigens, interleukin-6, IL-4, TNF-α, NF-κB, diabetes complications
- MeSH terms
- Diabetes Mellitus, Type 2, Female, Humans, Immunoglobulin G, Male, Middle Aged, Protein Binding, Protein Conformation, Serum Albumin, Substrate Specificity, Glycation End Products, Advanced, Molecular Docking Simulation
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