Objectives ANA-associated RMDs (ANA-RMDs—SLE, pSS, scleroderma, inflammatory myositis, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease) are a disease spectrum with overlapping clinical and immunological features. Musculoskeletal inflammation is common and impactful across ANA-RMDs. We evaluated musculoskeletal inflammation (ANA-arthritis) prevalence in a multi-disease ANA-RMD study, assessed its clinical impact across ANA-RMD diagnoses, proposed new basket groupings of patients and evaluated immunological profiles in legacy and new basket contexts. Methods An observational study enrolled ANA-RMD patients. Demographic variables, comorbidities, therapies, disease activity instruments (BILAG, SLEDAI, ESSDAI, physician-VAS), patient-reported outcomes (SF36, FACIT-Fatigue, EQ5D, ICECAP-A, WPAI, patient-VAS) and biomarker profile (6 gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian Mixture Modelling (GMM). Clinical and immune features of new and legacy clusters were compared. Results Inflammatory MSK symptoms were prevalent across ANA-RMDs, in 213/294 patients. In ANA-arthritis patients, most variables did not differ between diagnoses, excluding EQ5D-5L index and mobility domains (lower in MCTD/pSS, both p< 0.05). Fibromyalgia and osteoarthritis prevalence were similar across diagnoses. Therapy use differed significantly, biologic use being greatest in SLE (p< 0.05). GMM yielded two multi-disease clusters; High-MSK disease activity (n = 89) and Low-MSK disease activity (n = 124). High-MSK disease activity contained all patients with active joint swelling and had significantly higher prednisolone usage, PGA and Sm/RNP/SmRNP/Chromatin positivity, Tetherin-MFI and Interferon Score-A activity; with numerically lower fibromyalgia and osteoarthritis prevalence. Conclusion We define ANA-Arthritis, a more clinically and immunologically homogeneous population than existing RMDs for trials, and a more prevalent population for therapies in the clinic.

中文翻译：

---

ANA 关节炎：篮子试验人群的临床和生物标志物特征


目标 ANA 相关 RMD（ANA-RMD — SLE、pSS、硬皮病、炎性肌炎、混合结缔组织病 (MCTD) 和未分化结缔组织病）是具有重叠临床和免疫学特征的疾病谱。肌肉骨骼炎症在 ANA-RMD 中很常见且具有影响力。我们在一项多疾病 ANA-RMD 研究中评估了肌肉骨骼炎症（ANA-关节炎）的患病率，评估了其对 ANA-RMD 诊断的临床影响，提出了新的患者篮子分组，并评估了传统和新篮子环境中的免疫学特征。方法 一项观察性研究纳入了 ANA-RMD 患者。人口统计变量、合并症、治疗方法、疾病活动工具（BILAG、SLEDAI、ESSDAI、医生-VAS）、患者报告的结果（SF36、FACIT-Fatigue、EQ5D、ICECAP-A、WPAI、患者-VAS）和生物标志物概况（6分析基因表达评分、流式细胞术、自身抗体谱）。重新聚类利用高斯混合模型 (GMM)。比较了新集群和旧集群的临床和免疫特征。结果 213/294 名患者中，炎症性 MSK 症状在 ANA-RMD 中普遍存在。在 ANA 关节炎患者中，大多数变量在诊断之间没有差异，不包括 EQ5D-5L 指数和活动域（MCTD/pSS 较低，均为 p< 0.05）。纤维肌痛和骨关节炎的患病率在不同诊断中相似。治疗的使用差异显着，SLE 中生物制剂的使用最多 (p< 0.05)。 GMM 产生了两个多疾病簇；高 MSK 疾病活动度 (n = 89) 和低 MSK 疾病活动度 (n = 124)。 高 MSK 疾病活动度包含所有患有活动性关节肿胀的患者，并且具有显着较高的泼尼松龙使用量、PGA 和 Sm/RNP/SmRNP/染色质阳性、Tetherin-MFI 和干扰素 Score-A 活性；纤维肌痛和骨关节炎的患病率较低。结论 我们将 ANA 关节炎定义为比现有 RMD 进行试验的临床和免疫学同质性更高的人群，也是临床治疗中更普遍的人群。