Autoantibodies are present before the clinical diagnosis of systemic sclerosis
Autoantibodies are present before the clinical diagnosis of systemic sclerosis
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DOI：
10.1371/journal.pone.0214202
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发表时间：
2019-03-26
期刊：
影响因子：
3.7
通讯作者：
Olson, Stephen W.
中科院分区：
文献类型：
--
作者：
Burbelo, Peter D.;Gordon, Sarah M.;Olson, Stephen W.
系统性硬化症(SSC)是一种异质性自身免疫性疾病，与皮肤、血管系统和内脏的血管功能障碍和纤维化改变有关。尽管血清学异常是SSc的重要诊断工具，但自身抗体是否先于临床诊断尚不清楚。在这里，我们调查了SSC诊断前自身抗体的存在，并评估了某些自身抗体是否可能与硬皮病肾脏危象(SRC)的未来发病有关，SRC是一种潜在的致命并发症。使用国防部血清库，对年龄、性别和种族匹配的16例SRC患者(SSC/SRC)和30例无SRC的SSC患者(SSC/非SRC)的存档、前瞻性收集的纵向血清样本进行自身抗体分析。75%(12/16)的SSC/SRC和40%(12/30)的SSC/no SRC在临床诊断前至少有一种自身抗体阳性(最早27.1年，平均为-7.4年)。虽然这两个疾病组都表现出针对自身抗原小组的异质性免疫反应特征，但SSC/SRC受试者显示出两个富集簇，其中一个具有高水平的抗Ro52和/或Ro60的自身抗体，另一个具有高水平的针对RNA聚合酶复合体的免疫反应。与SSC/SRC中较大的免疫反应性和升高的自身抗体水平相一致，从血清阳性受试者最后一个时间点对自身抗原小组的总反应显示，与SSC/非SRC相比，SSC/SRC队列中包含更高的抗体水平(p=0.02)。总体而言，我们的研究结果表明，相关的血清阳性自身抗体通常先于SSC/NO SRC和SSC/SRC的临床诊断。
Systemic sclerosis (SSc) is a heterogeneous autoimmune disorder associated with vascular dysfunction and fibrotic changes in the skin, vasculature and internal organs. Although serologic abnormalities are an important diagnostic tool for SSc, little is known about whether autoantibodies precede clinical diagnosis. Here we investigated the presence of autoantibodies before SSc diagnosis and assessed whether certain autoantibodies might associate with the future onset of scleroderma renal crisis (SRC), a potentially fatal complication of the disease. Using the Department of Defense Serum Repository, autoantibodies were analyzed from archived, prospectively collected, longitudinal serum samples from sixteen individuals with SRC (SSc/SRC) and thirty cases of SSc without SRC (SSc/no SRC), matched for age, sex, and race. Seventy five percent (12/16) of the SSc/SRC and 40% (12/30) of the SSc/no SRC were seropositive for at least one autoantibody prior to clinical diagnosis (up to 27.1 years earlier, mean = -7.4 years). Although both disease groups demonstrated a heterogeneous immunoreactivity profile against the autoantigen panel, the SSc/SRC subjects showed two enriched clusters with one featuring elevated levels of autoantibodies against Ro52 and/or Ro60 and another with high levels of immunoreactivity against the RNA polymerase complex. Consistent with larger spectrum of immunoreactivity and the elevated levels of autoantibodies in SSc/SRC, the total response against the autoantigen panel from the last time point of the seropositive subjects revealed that the SSc/SRC cohort harbored higher antibody levels (p = 0.02) compared to SSc/no SRC. Overall, our findings demonstrate that relevant seropositive autoantibodies often precede the clinical diagnosis of SSc/no SRC and SSc/SRC.