Epitope-Based Chicken-Derived Novel Anti-PAD2 Monoclonal Antibodies Inhibit Citrullination.

Autor: Aosasa M; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Hossain MS; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Sakata T; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Koga K; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Shigemitsu T; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Shoya Y; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Yamaguchi M; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Saito K; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.; International PAD Research Center, 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan., Kim M; Pharma Foods International Co. Ltd., 1-49 Goryo-Ohara, Nishikyo Ku, Kyoto 615-8245, Japan.
Jazyk: angličtina
Zdroj: Journal of immunology research [J Immunol Res] 2021 Apr 12; Vol. 2021, pp. 6659960. Date of Electronic Publication: 2021 Apr 12 (Print Publication: 2021).
DOI: 10.1155/2021/6659960
Abstrakt: The aberrant upregulation of protein arginine deiminase 2- (PAD2-) catalyzed citrullination is reported in various autoimmune diseases (rheumatoid arthritis and multiple sclerosis) and several cancers. Currently, there are no anti-PAD2 monoclonal antibodies (mAbs) that can inhibit the citrullination reaction. Here, an epitope 341 YLNRGDRWIQDEIEFGY 357 was examined as an antigenic site of PAD2. Chickens were immunized with this epitope, and the generated mAbs were screened for its reactivity against the full-length PAD2. Enzyme-linked immunosorbent assay revealed that six mAbs, which were screened from the phage display library, crossreacted with mouse PAD2. Kinetic analysis revealed that mAbs are bound to PAD2 in the nanomolar range, which indicated a strong binding. Results of the in vitro citrullination inhibition assay revealed that the half-maximal effective concentration values of mAbs for the inhibition of histone or benzoyl-L-arginine ethyl ester citrullination were in the range of 6-75 nM which supports strong inhibition capabilities. Alanine scanning of epitope revealed that the peptide fragment 344 RGDRWIQDEIEF 355 was responsible for generating strong antibody responses that inhibit the PAD2-catalyzed citrullination reaction. These antibodies can aid in understanding the extracellular PAD2 function and treating diseases associated with aberrant citrullination.
Competing Interests: MA, MSH, TS, KK, TS, YS, MY, KS, and MK are employees of Pharma Foods International Co. Ltd.
(Copyright © 2021 Masayoshi Aosasa et al.)
Databáze: MEDLINE
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