Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues

International Journal of Molecular Sciences
Kutty Selva Nandakumar

Abstract

Rheumatoid arthritis (RA) is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies) are present in RA patients' sera for a long time before the onset of clinical disease. Prior to arthritis onset, in the autoantibody response, epitope spreading, avidity maturation, and changes towards a pro-inflammatory Fc glycosylation phenotype occurs. Genetic association of epitope specific autoantibody responses and the induction of inflammation dependent and independent changes in the cartilage by pathogenic autoantibodies emphasize the crucial contribution of antibody-initiated inflammation in RA development. Targeting IgG by glyco-engineering, bacterial enzymes to specifically cleave IgG/alter N-linked Fc-glycans at Asn 297 or blocking the downstream effector pathways offers new avenues to develop novel therapeutics for arthritis treatment.

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Citations

Apr 17, 2019·International Journal of Molecular Sciences·Chih-Hsin Tang
Nov 28, 2019·Mediators of Inflammation·Qinghua FangKutty Selva Nandakumar
Aug 6, 2020·International Journal of Molecular Sciences·Yuliya V MarkinaAlexander N Orekhov
Mar 20, 2019·International Journal of Molecular Sciences·Shyi-Jou ChenHuey-Kang Sytwu
Apr 8, 2020·Mediators of Inflammation·Qinghua FangKutty Selva Nandakumar

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Methods Mentioned

BETA
glycosylation

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