Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
RMD Open. 2023 Feb;9(1). doi: 10.1136/rmdopen-2022-002827.
Early diagnosis of systemic sclerosis (SSc) is important to start therapeutic interventions timely. Important risk factors for progression to SSc are the SSc-specific autoantibodies, of whom anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are the most frequent. ATA is associated with a severe disease course. A more detailed characterisation of the ATA-response in SSc might increase insights in preclinical disease stages and improve prognostication. To address this we identified all patients with suspected very early ATA-positive SSc, defined as all patients who are ATA-positive not fulfilling American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria, in the Leiden Combined Care in Systemic Sclerosis (CCISS)-cohort and found very low numbers.
This triggered us to search the literature on the ATA prevalence in patients with suspected very early SSc and contribution of the SSc-specific autoantibodies to progression from suspected very early to definite SSc. To increase insights on the ATA-response in suspected very early SSc, we then evaluated the association between the ATA-response and time between onset of Raynaud's phenomenon (RP) and first non-RP symptom, as a proxy for progressing to definite SSc, in all patients with ATA-positive SSc from the Leiden CCISS-cohort.
In short, included studies show that prevalence of ATA is much lower in suspected very early SSc than in populations fulfilling ACR/EULAR 2013 criteria. After 1-15 years of follow-up, only 52% of the patients with suspected very early SSc progress to definite SSc. ATA-IgG levels tend to be higher in patients with ATA-positive SSc with more rapid disease progression.
Although a role of ATA in disease progression is suggested, more studies on the ATA response in suspected very early SSc are warranted.
早期诊断系统性硬化症（SSc）对于及时开始治疗干预非常重要。进展为 SSc 的重要危险因素是 SSc 特异性自身抗体，其中抗着丝点抗体（ACA）和抗拓扑异构酶 I 抗体（ATA）最为常见。ATA 与严重的疾病过程相关。对 SSc 中 ATA 反应的更详细描述可能会增加对临床前疾病阶段的了解，并改善预后。为了解决这个问题，我们在莱顿联合系统性硬化症护理（CCISS）队列中确定了所有疑似早期 ATA 阳性 SSc 的患者，这些患者定义为 ATA 阳性但不符合美国风湿病学会（ACR）/欧洲抗风湿病联盟（EULAR）2013 标准的患者，并发现数量非常少。
这促使我们在文献中搜索疑似早期 SSc 患者中 ATA 的患病率以及 SSc 特异性自身抗体对从疑似早期到明确 SSc 的进展的贡献。为了增加对疑似早期 SSc 中 ATA 反应的了解，我们评估了 ATA 反应与雷诺现象（RP）发作和首个非 RP 症状之间的时间关系，在莱顿 CCISS 队列中的所有 ATA 阳性 SSc 患者中，这是进展为明确 SSc 的一个替代指标。
简而言之，纳入的研究表明，疑似早期 SSc 中的 ATA 患病率远低于符合 ACR/EULAR 2013 标准的人群。在 1-15 年的随访中，只有 52%的疑似早期 SSc 患者进展为明确 SSc。在疾病进展较快的 ATA 阳性 SSc 患者中，ATA-IgG 水平往往较高。
尽管 ATA 在疾病进展中的作用被认为是有意义的，但仍需要更多关于疑似早期 SSc 中 ATA 反应的研究。
