Cuervo Andrea, Celis Raquel, Julià Antonio, Usategui Alicia, Faré Regina, Ramírez Julio, Azuaga Ana Belen, Lorenzo Andrés, Sanmartí Raimon, Pablos José L, Cañete Juan D
Arthritis Unit, Department of Rheumatology, Hospital Clínic, University of Barcelona and Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
Front Med (Lausanne). 2021 Apr 9;8:656667. doi: 10.3389/fmed.2021.656667. eCollection 2021.
Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA. DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns. One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3 T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found. Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.
未分化关节炎（UA）被定义为一种不符合明确诊断标准的炎性关节炎。延迟做出特定诊断和治疗可能会导致功能预后受损。我们的目的是确定与UA患者明确诊断分类相关的滑膜生物标志物。纳入了未使用过改善病情抗风湿药（DMARD）且有可用初始滑膜组织（ST），并在随访期间最终诊断为类风湿关节炎（RA）或银屑病关节炎（PsA）的UA患者，并与明确诊断疾病（RA或PsA）的患者进行比较。比较了两组之间的临床、关节镜和病理数据。病理学包括对细胞类型和人类干扰素调节的Mx A进行定量免疫组织化学（IHC）分析。进行主成分分析（PCA）以提取疾病模式。共纳入105例患者：31例未使用过DMARD的UA患者（在中位7年的随访期间，19例发展为RA，12例发展为PsA），39例确诊RA患者，35例确诊PsA患者。与确诊RA和PsA组相比，UA组的ST显示巨噬细胞密度更高。与确诊RA相比，发展为RA的UA患者（UA-RA）显示Mx A表达和CD3 T细胞密度更高。与确诊PsA相比，发展为PsA的UA患者（UA-PsA）显示血管生成增加和滑膜衬里成纤维细胞密度增加。与UA-RA相比，UA-PsA患者的滑膜炎显示更多肥大细胞和衬里成纤维细胞。未发现局部或全身炎症标志物存在组间差异。我们的结果显示，与RA和PsA相比，UA滑膜的细胞组成存在差异，UA组的细胞浸润密度更高。干扰素诱导基因Mx A的初始表达可能是进展为RA的生物标志物，而更高的肥大细胞和成纤维细胞密度可能与PsA进展相关。
