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Int. J. Mol. Sci. 2018, 19(3), 677; https://doi.org/10.3390/ijms19030677

Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues

1
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510000, China
2
Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden
Received: 31 December 2017 / Revised: 25 January 2018 / Accepted: 22 February 2018 / Published: 28 February 2018
(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis)
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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. View Full-Text
Keywords: rheumatoid arthritis; antibodies; collagen; glycosylation; disease pathways; therapy; experimental arthritis rheumatoid arthritis; antibodies; collagen; glycosylation; disease pathways; therapy; experimental arthritis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Nandakumar, K.S. Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues. Int. J. Mol. Sci. 2018, 19, 677.

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