Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency

• Published in: Arthritis research & therapy Vol. 22; no. 1; p. 248
• Main Authors: Iwasaki, Takeshi, Nakabo, Shuichiro, Terao, Chikashi, Murakami, Kosaku, Nakashima, Ran, Hashimoto, Motomu, Imura, Yoshitaka, Yukawa, Naoichiro, Yoshifuji, Hajime, Miura, Yasuo, Yurugi, Kimiko, Maekawa, Taira, van Delft, Myrthe A. M, Trouw, Leendert A, Fujii, Takao, Mimori, Tsuneyo, Ohmura, Koichiro
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 19.10.2020; BioMed Central; BMC
• Subjects: Anti-cyclic citrullinated peptide antibody; Antigenic determinants; Arthritis; Connective tissue disease; Enzyme-linked immunosorbent assay; HLA antigens; Medical research; Peptides; Rheumatoid arthritis; Rheumatoid factor; Shared epitope
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-020-02351-4

Abstract Background The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. Methods In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients. Results Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. Conclusions Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.