■系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征是多种疾病症状和不可预测的临床病程。为了改善治疗结果,根据SLE患者常见的免疫学表现进行分层,如自身抗体,I型干扰素(IFN)签名和中性粒细胞胞外诱捕网(NET)的释放可能有所帮助。假设这些免疫学现象之间存在关联,因为NET释放诱导IFN产生并且IFN通过B细胞活化诱导自身抗体形成。在这里,我们研究了自身抗体之间的关联,IFN签名,NET版本,SLE患者的临床表现。
■我们对25例SLE患者的57例SLE相关自身抗体进行了主成分分析(PCA)和层次聚类。我们将每种自身抗体与IFN标签和NET诱导能力相关联。
■我们观察到两个不同的簇:一个簇主要包含具有高IFN特征的患者。这种类型的患者通常会出现皮肤狼疮,并具有较高的抗dsDNA浓度。另一簇包含具有高和低IFN特征的患者的混合。NET诱导能力高和低的患者在集群之间分布相等。簇之间的差异主要由针对组蛋白的抗体驱动,RibP2,RibP0,EphB2,RibP1,PCNA,dsDNA,和核小体。此外,我们发现,在有IFN标记的患者中,抗EphB2,RibP1和RNP70的自身抗体浓度有增加的趋势.我们发现NET诱导能力与抗FcER(r=-0.530;p=0.007)和抗PmScl100(r=-0.445;p=0.03)呈负相关。
■我们确定了一组具有IFN特征的患者,这些患者表达了针对DNA和RNA结合蛋白的抗体浓度增加,这可以用于进一步的患者分层和更有针对性的治疗。我们没有发现自身抗体和NET诱导能力之间的正相关。我们的研究进一步加强了RNA结合自身抗体和IFN标签之间相关性的证据。
UNASSIGNED: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE.
UNASSIGNED: We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity.
UNASSIGNED: We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = -0.530; p = 0.007) and anti-PmScl100 (r = -0.445; p = 0.03).
UNASSIGNED: We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature.