Centre for Rheumatology and Connective Tissue Diseases, Division of Medicine, University College London, London, UK.
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
Sci Rep. 2022 Jul 2;12(1):11212. doi: 10.1038/s41598-022-15062-4.
Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients' clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease's features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with > 1 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had ≥ 2 autoantibody positivity, and 2.3% (n = 72) had ≥ 2 SSc-Abs positivity. Th e most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.
系统性硬化症（SSc）的特征是存在 SSc 特异性或 SSc 相关抗体（SSc-Ab）：抗拓扑异构酶 I（ATA）、抗着丝粒（ACA）、抗 RNA 聚合酶 III（ARA）、抗 U3RNP（U3RNP）、抗 U1RNP（U1RNP）、抗 PmScl（PmScl）、抗 Ku（Ku）和抗 Th/To（Th/To），每种抗体都与特定的临床特征和预后相关。在 SSc 患者中检测到一种以上的 SSc-Ab 较为罕见，目前仅有少数关于这些患者临床表型的数据。我们的研究旨在评估在一个大型 SSc 患者队列中，存在>1 种 SSc-Ab 阳性的频率以及与该情况相关的疾病特征。回顾性分析了 2001 年 2 月至 2017 年 6 月期间 2799 例 SSc 患者的自身抗体谱。确定了存在>1 种 SSc-Ab 的患者。收集了临床特征，并与具有单种 SSc-Ab 阳性的大型 SSc 患者历史队列进行比较。如果患者曾接受利妥昔单抗、静脉注射免疫球蛋白或干细胞移植治疗，则将其排除在外。使用非参数检验进行统计分析。我们队列中的近 5%的 SSc 患者存在≥2 种自身抗体阳性，2.3%（n=72）存在≥2 种 SSc-Ab 阳性。最常见的组合是 U1RNP 和 ATA（35%）。这些患者比单种自身抗体阳性的患者年轻，更常见弥漫性皮肤 SSc 形式。与 ATA 患者相比，他们也有更高的重叠特征发生率。其他组合包括 U1RNP 和 ACA（13%）、ATA 和 ACA（7%）以及 U1RNP 和 PmScl（5%）。在我们的研究中，我们观察到，尽管不常见，但 SSc 患者可能同时存在两种 SSc-Ab，并且与单种 SSc-Ab 阳性患者相比，双阳性可能影响其临床表型。还强调了在临床表型发生变化的患者中重新检测 SSc-Ab 的重要性，因为这可能会带来不同的风险分层。
