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AGE/Non-AGE Glycation: An Important Event in Rheumatoid Arthritis Pathophysiology

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Abstract—

Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease that gradually affects the synovial membrane and joints. Many intrinsic and/or extrinsic factors are crucial in making RA pathology challenging throughout the disease. Substantial enzymatic or non-enzymatic modification of proteins driving inflammation has gained a lot of interest in recent years. Endogenously modified glycated protein influences disease development linked with AGEs/non-AGEs and is reported as a disease marker. In this review, we summarized current knowledge of the differential abundance of glycated proteins by compiling and analyzing a variety of AGE and non-AGE ligands that bind with RAGE to activate multi-faceted inflammatory and oxidative stress pathways that are pathobiologically associated with RA-fibroblast-like synoviocytes (RA-FLS). It is critical to comprehend the connection between oxidative stress and inflammation generation, mediated by glycated protein, which may bind to the receptor RAGE, activate downstream pathways, and impart immunogenicity in RA. It is worth noting that AGEs and non-AGEs ligands play a variety of functions, and their functionality is likely to be more reliant on pathogenic states and severity that may serve as biomarkers for RA. Screening and monitoring of these differentially glycated proteins, as well as their stability in circulation, in combination with established pre-clinical characteristics, may aid or predict the onset of RA.

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Acknowledgements

We acknowledge Council of Scientific and Industrial Research (CSIR), and Department of Science and Technology, Government of India, New Delhi, India, for providing financial support. Mr Monu received fellowship support from CSIR, New Delhi. Ms Prachi Agnihotri received fellowship from DST-SERB project GAP0212. We also thank Council of Scientific and Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, Delhi, India, for research and Academy of Scientific and Innovative Research (AcSIR), India for the academic support.

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We would like to acknowledge the Science and Engineering Research Board-Department of Science and Technology (SERB-DST), New Delhi, India, for financial support.

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    Monu, Prachi Agnihotri & Sagarika Biswas

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Monu

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Monu drafted the manuscript. Monu, Prachi Agnihotri, and Dr. Sagarika Biswas edited and revised the manuscript. All authors read and approved the final manuscript.

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Monu, Agnihotri, P. & Biswas, S. AGE/Non-AGE Glycation: An Important Event in Rheumatoid Arthritis Pathophysiology. Inflammation 45, 477–496 (2022). https://doi.org/10.1007/s10753-021-01589-7

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