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Rheumatoid arthritis–specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen

Abstract : OBJECTIVE: Autoantibodies to citrullinated proteins are specific for rheumatoid arthritis (RA) and recognize epitopes centered by citrulline, a posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4 (PAD-4), the enzyme that converts arginine into citrulline, is in itself a target for RA-specific autoantibodies. This study was undertaken to assess whether anti-PAD-4 autoantibodies interfere with citrullination in vitro in patients with RA, and to identify peptide targets of anti-PAD-4 antibodies that can activate or inhibit citrullination. METHODS: To test whether autoantibodies to PAD-4 influence citrullination, an in-house citrullination assay was developed using purified autoantibodies to PAD-4. To map B cell epitopes on PAD-4, 65 overlapping 20-mer peptides encompassing the entire PAD-4 were analyzed for their reactivity in RA sera. RESULTS: Autoantibodies to PAD-4 inhibited PAD-4-mediated citrullination. Three linear peptides on PAD-4 were recognized almost uniquely by PAD-4 autoantibodies in the sera of patients with RA. One peptide was located in the N-terminal, calcium-binding domain of PAD-4, while 2 other peptides were located in the C-terminal, substrate-binding domain of PAD-4. CONCLUSION: Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4. Most anti-PAD-4-positive sera recognize peptides located both in the N-terminal domain (211-290) and the C-terminal domain (601-650) of PAD-4.
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https://www.hal.inserm.fr/inserm-02440901
Contributor : Isabelle Auger <>
Submitted on : Wednesday, January 15, 2020 - 3:02:41 PM
Last modification on : Thursday, January 16, 2020 - 1:37:49 AM

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Isabelle Auger, Marielle Martin, Nathalie Balandraud, Jean Roudier. Rheumatoid arthritis–specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen. Arthritis and Rheumatism, Wiley, 2010, 62 (1), pp.126-131. ⟨10.1002/art.27230⟩. ⟨inserm-02440901⟩

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