Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis

Wakako Sakaguchi; Juri Saruta; Yuko Yamamoto; Tomoko Shimizu; Shinya Fuchida; Keiichi Tsukinoki

doi:10.1016/j.job.2024.03.007

Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis

J Oral Biosci. 2024 Mar 28:S1349-0079(24)00076-8. doi: 10.1016/j.job.2024.03.007. Online ahead of print.

Authors

Wakako Sakaguchi¹, Juri Saruta², Yuko Yamamoto³, Tomoko Shimizu⁴, Shinya Fuchida⁵, Keiichi Tsukinoki⁶

Affiliations

¹ Department of Pathology and Histomorphology, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. Electronic address: sakaguchi@kdu.ac.jp.
² Department of Education Planning, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. Electronic address: saruta@kdu.ac.jp.
³ Department of Dental Hygiene, Kanagawa Dental University, Junior College, 82 Inaoka, Yokosuka, Kanagawa 2388580, Japan. Electronic address: yamamoto.yuko@kdu.ac.jp.
⁴ Department of Implantology and Periodontology, Kanagawa Dental University, 3-31-6 Tsuruya, Kanagawa-ku, Yokohama 2210835, Kanagawa, Japan. Electronic address: shimizu@kdu.ac.jp.
⁵ Department of Education Planning, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. Electronic address: fuchida@kdu.ac.jp.
⁶ Department of Pathology and Histomorphology, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. Electronic address: tsukinoki@kdu.ac.jp.

PMID: 38554831
DOI: 10.1016/j.job.2024.03.007

Abstract

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive joint destruction. Early diagnosis and treatment, before joint deformation or destruction occurs, are crucial. Identifying novel biomarkers for RA in saliva could potentially enable early detection of the disease, prior to its onset.

Methods: We conducted a comprehensive proteomic analysis of salivary proteins in a mouse model of RA. Proteins were identified using western blotting and enzyme-linked immunosorbent assay in the serum, saliva, and ankle joints of DBA/1JJmsSlc mice, a model of RA. Ankle joints and submandibular glands were stained with hematoxylin and eosin and immunostained, and the results were compared with those of control mice.

Results: Citrullinated alpha-1 antitrypsin (A1AT, 46 kDa) was commonly detected in the saliva, serum, and ankle joints of mice with severe RA and was confirmed through proteomic analysis. Western blotting showed a band corresponding to 46 kDa in the serum, saliva, and ankle joints. Immunostaining of the ankle joints with the A1AT antibody showed a strong positive signal in the synovium.

Conclusions: In DBA/1JJmsSlc mice, cyclic citrullinated peptide antibodies and A1AT may be involved in citrullination and contribute to the development and severity of RA, making them valuable treatment targets requiring further study.

Keywords: A1AT; DBA/1JJmsSlc mice; Proteomic analysis; RA; Saliva.