Royal National Hospital for Rheumatic Diseases, Royal United Hospitals NHS Foundation Trust, University of Bath, Bath, UK.
Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
Rheumatology (Oxford). 2018 Apr 1;57(4):712-717. doi: 10.1093/rheumatology/kex458.
Autoantibodies targeting ubiquitously expressed nuclear antigens can be identified in most patients with SSc. Cytoplasmic autoantibodies (in otherwise ANA-negative sera) targeting eukaryotic initiation factor-2B (anti-eIF2B) have recently been identified in SSc with clinical associations to dcSSc disease and interstitial lung disease (ILD), although the majority of samples originated from a tertiary SSc-ILD centre. We investigated the prevalence and clinical associations of recently described SSc-specific (including anti-eIF2B) and other cytoplasmic autoantibodies in ANA-negative sera obtained from a large representative SSc cohort.
ANA-negative sera from the Scleroderma Family Registry and DNA Repository underwent indirect immunofluorescence, radiolabelled protein immunoprecipitation (± immunodepletion) to identify anti-eIF2B and other CTD-related autoantibodies. The clinical phenotype of positive samples was evaluated.
Immunoprecipitation was performed on 128 ANA-negative samples (obtained from 3249 SSc patients). Anti-eIF2B antibodies were present in nine patients (7%), the majority of whom had dcSSc (8/9). SSc-ILD was present in all anti-eIF2B patients for whom chest imaging was available (7/9). Anti-synthetase autoantibodies (targeting PL12, PL7, OJ and Zo) were identified in seven patients (5.5%), all of whom fulfilled the 2013 ACR/EULAR classification criteria for SSc and had evidence of SSc-ILD where relevant outcomes were available for evaluation. Anti-RuvBL1/2 antibodies were identified in two patients with SSc-overlap syndromes.
Anti-eIF2B antibodies are cytoplasmic SSc-specific autoantibodies with strong clinical associations with dcSSc and SSc-ILD found in ANA-negative sera. Anti-synthetase autoantibodies, and other recently discovered SSc-specific antibodies such as anti-RuvBL1/2, can also be identified in ANA-negative SSc.
针对广泛表达的核抗原的自身抗体可在大多数 SSc 患者中检测到。细胞质自身抗体（在其他 ANA 阴性血清中）针对真核起始因子-2B（抗-eIF2B）最近在 SSc 中被鉴定出来，与 dcSSc 疾病和间质性肺病（ILD）有关，尽管大多数样本来自一个三级 SSc-ILD 中心。我们研究了在从大型代表性 SSc 队列获得的 ANA 阴性血清中，最近描述的 SSc 特异性（包括抗-eIF2B）和其他细胞质自身抗体的患病率和临床关联。
从硬皮病家族登记和 DNA 库中获得 ANA 阴性血清，进行间接免疫荧光、放射性标记蛋白免疫沉淀（±免疫耗竭）以鉴定抗-eIF2B 和其他 CTD 相关自身抗体。评估阳性样本的临床表型。
对 128 份 ANA 阴性样本（来自 3249 名 SSc 患者）进行了免疫沉淀。在 9 名患者（7%）中存在抗-eIF2B 抗体，其中大多数为 dcSSc（8/9）。所有可获得胸部影像学资料的抗-eIF2B 患者均存在 SSc-ILD（7/9）。在 7 名患者（5.5%）中鉴定出抗合成酶自身抗体（针对 PL12、PL7、OJ 和 Zo），他们均符合 2013 年 ACR/EULAR SSc 分类标准，并且在相关结果可用于评估的情况下存在 SSc-ILD。在两名 SSc 重叠综合征患者中鉴定出抗 RuvBL1/2 抗体。
抗-eIF2B 抗体是细胞质 SSc 特异性自身抗体，在 ANA 阴性血清中与 dcSSc 和 SSc-ILD 具有强烈的临床关联。抗合成酶自身抗体以及其他最近发现的 SSc 特异性抗体，如抗 RuvBL1/2，也可以在 ANA 阴性的 SSc 中被鉴定出来。
