Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Chiba, Japan.
Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Chiba, Japan.
PLoS One. 2021 May 21;16(5):e0252116. doi: 10.1371/journal.pone.0252116. eCollection 2021.
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).
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.
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).
Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.
我们旨在探讨肌肉骨骼炎症模式与外周血固有淋巴细胞（ILC）群体、血清细胞因子/趋化因子以及甲氨蝶呤治疗反应之间的关联，这些关联存在于类风湿关节炎（RA）和脊柱关节炎（SpA）患者中。
我们招募了 100 名 RA 或 SpA 患者，并进行超声检查以评估滑膜炎（52 个关节部位）、腱鞘炎（20 根肌腱）和肌腱附着点炎（44 个部位）的功率多普勒信号。我们使用基于无监督随机森林的聚类分析，根据多轴超声信息对患者进行分组，并通过流式细胞术鉴定和计数外周血中的 ILC1-3 群体，同时测量 20 种细胞因子/趋化因子的血清水平。我们还在 38 名接受甲氨蝶呤治疗的患者中评估了 3 个月时的 ACR20 反应。
与 SpA 相比，RA 中滑膜炎更为常见且严重，而腱鞘炎和肌腱附着点炎在 RA 和 SpA 之间相似。患者被分为两组，代表滑膜炎为主和滑膜炎非为主的炎症模式。虽然 RA 和 SpA 之间的外周 ILC 计数没有显著差异，但在滑膜炎非为主组中明显高于滑膜炎为主组（ILC1-3：p=0.0007、p=0.0061 和 p=0.0002）。另一方面，基于血清细胞因子/趋化因子对患者进行聚类分析，既不能明确对应临床诊断，也不能对应滑膜炎为主/非为主模式。滑膜炎为主模式是预测甲氨蝶呤临床反应的最显著因素（p=0.0065）。
超声确定的肌肉骨骼炎症模式与外周血 ILC 计数相关，并可预测甲氨蝶呤的治疗反应。
