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.

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.

• Authors: Takeshi Iwasaki, Shuichiro Nakabo, Chikashi Terao, Kosaku Murakami, Ran Nakashima, Motomu Hashimoto, Yoshitaka Imura, Naoichiro Yukawa, Hajime Yoshifuji, Yasuo Miura, Kimiko Yurugi, Taira Maekawa, Myrthe A M van Delft, Leendert A Trouw, Takao Fujii, Tsuneyo Mimori, Koichiro Ohmura
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 22 Issue 1 Pg. 248 (10 19 2020) ISSN: 1478-6362 [Electronic] England
• PMID: 33076960 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• HLA-DRB1 Chains
• Peptides, Cyclic

Topics

• Alleles
• Arthritis, Rheumatoid (diagnosis, genetics)
• Autoantibodies
• Citrullination
• Follow-Up Studies
• HLA-DRB1 Chains (genetics)
• Humans
• Peptides, Cyclic
• Retrospective Studies