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Preventing joint destruction is one of the challenges in rheumatoid arthritis (RA).1 Presence of two antibodies, namely, rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (CCPs), is one of the major correlates of joint destruction.2 We recently showed the association between the progression of joint destruction and HLA-DRB1*04:05, which is independent from CCP positivity.3 HLA-DRB1*04:05 is one of shared epitope (SE) allele carrying common amino acid sequences at position 70–74 frequently found in Japanese and rarely observed in Europeans. Importantly, we showed that SE alleles other than DRB1*04:05 did not show independent associations from CCP.3
Based on the unique characteristics of HLA-DRB1*04:05, we hypothesised that HLA-DRB1*04:05 might lead to high disease activity not fully captured by Disease Activity Acore 28 (DAS28) and that it independently of DAS28 determines radiographic progression in patients with anti-CCP-positive RA (figure 1A).
Handling editor Josef S Smolen
Contributors CT conceived the study design. HT and CT analysed the data. HT and CT wrote the main manuscript text. KY, KI, MH, MF, HI, TF, KO, AT, HY and TM contributed to collection of samples and/or data. KY and MF counted SHS score for the IORRA and KURAMA, respectively. WY aggregated the KURAMA database. All authors reviewed the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Kyoto University Graduate School of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.
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