Objectives ANA-associated rheumatic and musculoskeletal (MSK) diseases (RMDs) [SLE, primary SS (pSS), scleroderma, inflammatory myositis, MCTD and UCTD] make up a disease spectrum with overlapping clinical and immunological features. MSK inflammation is common and impactful across ANA-associated RMDs. The objectives of this study were to evaluate MSK inflammation (ANA-associated arthritis) prevalence in a multidisease ANA-associated RMD study, assess its clinical impact across ANA-associated RMD diagnoses, propose new basket groupings of patients, and evaluate immunological profiles in legacy and new basket contexts. Methods An observational study enrolled patients with ANA-associated RMDs. Demographic variables, comorbidities, therapies, disease activity instruments [BILAG, SLEDAI, the EULAR SS disease activity index (ESSDAI), physician visual analogue scale (VAS)], patient-reported outcomes [SF36, FACIT-Fatigue, EQ5D, ICECAP-A, Work Productivity and Activity impairment (WPAI), patient VAS] and the biomarker profile (six-gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian mixture modelling (GMM). The clinical and immune features of new and legacy clusters were compared. Results Inflammatory MSK symptoms were prevalent across ANA-associated RMDs, in 213/294 patients. In ANA-associated arthritis patients, most variables did not differ between diagnoses, with the exception of the EQ5D-5L index and mobility domains (lower in MCTD/pSS, both P < 0.05). FM and OA prevalence were similar across diagnoses. Therapy use differed significantly, the use of biologics being greatest in SLE (P < 0.05). GMM yielded two multidisease clusters: High MSK disease activity (n = 89) and low MSK disease activity (n = 124). The high MSK disease activity cluster included all patients with active joint swelling, and they had significantly higher prednisolone usage, physician global assessment (PGA), Sm/RNP/SmRNP/chromatin positivity, Tetherin mean fluorescence intensity (MFI), and IFN Score-A activity, along with numerically lower FM and OA prevalence. Conclusion We defined ANA-associated arthritis, a more clinically and immunologically homogeneous population than existing RMD populations for trials, and a more prevalent population for therapies in the clinic.

中文翻译：

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ANA 相关关节炎：篮子试验人群的临床和生物标志物特征


目的 ANA 相关的风湿和肌肉骨骼 （MSK） 疾病 （RMD） [SLE、原发性 SS （pSS）、硬皮病、炎性肌炎、MCTD 和 UCTD] 构成了具有重叠临床和免疫学特征的疾病谱。MSK 炎症在 ANA 相关 RMD 中很常见且有影响。本研究的目的是在一项多疾病 ANA 相关 RMD 研究中评估 MSK 炎症（ANA 相关关节炎）的患病率，评估其对 ANA 相关 RMD 诊断的临床影响，提出新的篮子患者分组，并评估传统和新篮子环境中的免疫学特征。方法 一项观察性研究招募了 ANA 相关 RMD 患者。分析人口统计变量、合并症、治疗、疾病活动工具 [BILAG、SLEDAI、EULAR SS 疾病活动指数 （ESSDAI）、医师视觉模拟量表 （VAS）]、患者报告的结果 [SF36、FACIT-疲劳、EQ5D、ICECAP-A、工作效率和活动障碍 （WPAI）、患者 VAS] 和生物标志物谱 （六基因表达评分、流式细胞术、自身抗体谱）。 重新聚类利用高斯混合建模 （GMM）。比较了新集群和旧集群的临床和免疫特征。结果 炎症性 MSK 症状在 ANA 相关 RMD 中普遍存在，在 213/294 例患者中。在 ANA 相关关节炎患者中，大多数变量在诊断之间没有差异，但 EQ5D-5L 指数和活动度域除外 （MCTD/pSS 较低，均 P < 0.05）。FM 和 OA 患病率在诊断中相似。治疗使用差异显著，生物制剂在 SLE 中的使用最大 （P < 0.05）。GMM 产生两个多疾病集群：高 MSK 疾病活动度 （n = 89） 和低 MSK 疾病活动度 （n = 124）。 高 MSK 疾病活动集群包括所有活动性关节肿胀患者，他们的泼尼松龙使用量、医师整体评估 （PGA）、Sm/RNP/SmRNP/染色质阳性、Tetherin 平均荧光强度 （MFI） 和 IFN 评分-A 活性，以及数值较低的 FM 和 OA 患病率。结论 我们定义了 ANA 相关关节炎，与现有的 RMD 试验人群相比，其临床和免疫学人群更加同质，并且临床治疗人群更普遍。