Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis

OBJECTIVES: We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment. RESULTS: Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065). CONCLUSIONS: Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.