Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study.
Shoichi Fukui, Tohru Michitsuji, Yushiro Endo, Ayako Nishino, Kaori Furukawa, Shimpei Morimoto, Toshimasa Shimizu, Masataka Umeda, Remi Sumiyoshi, Tomohiro Koga, Naoki Iwamoto, Mami Tamai, Tomoki Origuchi, Karin A J van Schie, Yukitaka Ueki, Nobutaka Eiraku, Tamami Yoshitama, Naoki Matsuoka, Takahisa Suzuki, Akitomo Okada, Hiroaki Hamada, Masahiro Ayano, Toshihiko Hidaka, Tomomi Tsuru, Takahiro Maeda, Tom W J Huizinga, René E M Toes, Atsushi Kawakami, Shin-Ya Kawashiri
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Abstract
Objectives: To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).
Patients and methods: We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.
Results: Dimensionality reduction using 38 cytokines and chemokines demonstrated four distinct clusters that differed significantly regarding the frequencies of remission defined by clinical composite measures and ultrasound evaluations. Prominent differences in IL-1β, IL-5, IL-7, IL-10, IFNγ, GRO, IP-10, MCP-1 and MIP-1β characterised the between-cluster differences. Two distinct groups made of four clusters showed a significant difference in IgM-anti-CCP2 positivity. The least absolute shrinkage and selection operator regression of 38 cytokines and chemokines for Clinical Disease Activity Index (CDAI) remission at 12 months resulted in the selection of MIP-1β. Logistic regression using baseline levels of anti-citrullinated protein antibody, IgM-anti-CCP2 positivity, the CDAI, the total power Doppler score, the cluster by cytokines and chemokines, MIP-1β, methotrexate dose and mechanisms of action revealed that cluster by cytokines and chemokines was the sole significant factor for CDAI remission at 12 months.
Conclusions: Specific patterns of cytokines and chemokines-no other clinical factors and autoantibody profiles-were important to distinguish patients with RA achieving remission at 12 months.
期刊介绍：
RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
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