目标:ANA相关RMDs(ANA-RMDs-SLE,PSS,硬皮病,炎性肌炎,混合性结缔组织病(MCTD)和未分化结缔组织病)是具有重叠的临床和免疫学特征的疾病谱。肌肉骨骼炎症在ANA-RMD中是常见且有影响的。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,评估了其在ANA-RMD诊断中的临床影响,提出了患者的新篮子分组,并评估了传统和新篮子环境中的免疫学概况。
方法:一项观察性研究纳入ANA-RMD患者。人口统计变量,合并症,疗法,疾病活动仪器(BILAG,SLEDAI,ESSDAI,physician-VAS),患者报告的结果(SF36,FACIT-疲劳,EQ5D,ICACAP-A,WPAI,patient-VAS)和生物标志物谱(6个基因表达评分,流式细胞术,自身抗体谱)进行了分析。回收利用高斯混合建模(GMM)。比较了新集群和遗留集群的临床和免疫特征。
结果:炎症性MSK症状在ANA-RMD中普遍存在,213/294名患者。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指数和移动域(MCTD/PSS中较低,两者p<0.05)。纤维肌痛和骨关节炎的患病率在诊断中相似。治疗方法的使用差异很大,SLE中生物使用最大(p<0.05)。GMM产生了两个多疾病簇;高MSK疾病活动性(n=89)和低MSK疾病活动性(n=124)。高MSK疾病活动包含所有活动性关节肿胀的患者,并且泼尼松龙的使用率明显更高,PGA和Sm/RNP/SmRNP/染色质阳性,Tetherin-MFI和干扰素评分-A活性;纤维肌痛和骨关节炎患病率较低。
结论:我们定义ANA-关节炎,与现有的试验用RMD相比,临床和免疫学上更同质的人群,以及临床上更普遍的治疗人群。
OBJECTIVE: 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.
CONCLUSIONS: 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.