Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, UK.
Systemic Autoimmune Diseases Research Unit Specialties Hospital UMAE-CIBIOR, Mexican Social Security Institute, Puebla, Mexico.
Autoimmun Rev. 2022 Nov;21(11):103184. doi: 10.1016/j.autrev.2022.103184. Epub 2022 Aug 27.
Undifferentiated connective tissue disease (UCTD) encapsulates a broad range of conditions including incomplete forms of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), some of whom progress to a formal clinical diagnosis over time. This systematic review (SR) and meta-analysis aimed to identify clinical and laboratory features and biomarkers that can predict progression of UCTD.
A systematic literature search was carried out on MEDLINE, EMBASE and the Cochrane Central Register of Randomized Controlled Trials. Abstracts and full-text manuscripts were screened by two reviewers. Publications were included if they included at least 20 UCTD patients, a minimum of six months of follow up, and provided data on at least one risk factor for developing a defined CTD. The QUIPS tool was used to assess risk of bias (RoB) and GRADE for grading the quality of the evidence. The study is registered with PROSPERO (ID: CRD42021237725).
Fifty-nine studies were included in the SR, and forty-one in the meta-analysis. The predictors for progression to SLE with the highest certainty of evidence included those with younger age (MD -5.96 [-11.05-0.87 years]), serositis (RR 2.69 [1.61-4.51]), or the presence of anti-dsDNA antibodies (RR 4.27 [1.92-9.51]). For SSc, the highest certainty of evidence included puffy fingers (RR [3.09 [1.48-6.43]), abnormal nailfold changes (NFC) (avascular areas [RR 5.71 (3.03-10.8)] or active or late SSc pattern [RR 2.24 (1.25-4.01)] and anti-topoisomerase-I (RR 1.83 [1.45-2.30]). No novel biomarkers were included in the meta-analysis; however HLA molecules, regulatory T cell shift, pro-inflammatory cytokines and complement activation products were identified as potential predictors for evolution of disease.
Clinical and immunological parameters may predict which patients with UCTD progress to definitive disease; however, the heterogeneous nature and RoB in most studies limits the ability to apply these results in routine clinical practice. Limited data suggest that some novel biomarkers may provide additional predictive value but these will need larger well designed studies to fully delineate their clinical utility.
未分化结缔组织病（UCTD）涵盖了广泛的疾病，包括不完全型系统性红斑狼疮（SLE）和系统性硬皮病（SSc），其中一些患者随着时间的推移会进展为明确的临床诊断。本系统评价（SR）和荟萃分析旨在确定能够预测 UCTD 进展的临床和实验室特征及生物标志物。
对 MEDLINE、EMBASE 和 Cochrane 中央对照试验注册库进行了系统文献检索。由两名评审员对摘要和全文进行筛选。如果研究纳入了至少 20 名 UCTD 患者、至少 6 个月的随访期，并提供了至少一个发展为明确 CTD 的风险因素的数据，则纳入研究。使用 QUIPS 工具评估偏倚风险（RoB），并使用 GRADE 评估证据质量。本研究已在 PROSPERO（注册号：CRD42021237725）注册。
本 SR 纳入了 59 项研究，41 项进行了荟萃分析。具有最高确定性证据的进展为 SLE 的预测因素包括年龄较小（MD-5.96[-11.05-0.87 岁]）、浆膜炎（RR 2.69[1.61-4.51]）或存在抗 dsDNA 抗体（RR 4.27[1.92-9.51]）。对于 SSc，具有最高确定性证据的预测因素包括肿胀的手指（RR[3.09[1.48-6.43]）、异常甲褶变化（NFC）（无血管区[RR 5.71[3.03-10.8]）或活动期或晚期 SSc 模式[RR 2.24[1.25-4.01]）和抗拓扑异构酶 I（RR 1.83[1.45-2.30]）。荟萃分析中未纳入新的生物标志物；然而，HLA 分子、调节性 T 细胞转移、促炎细胞因子和补体激活产物被确定为疾病进展的潜在预测因素。
临床和免疫学参数可能预测哪些 UCTD 患者会进展为明确疾病；然而，大多数研究的异质性和 RoB 限制了将这些结果应用于常规临床实践的能力。有限的数据表明，一些新的生物标志物可能提供额外的预测价值，但这些需要更大规模、设计良好的研究来充分阐明其临床实用性。
