自身抗体与系统性红斑狼疮患者 IFN 特征和 NETosis 的关系

IF 4.7 Q2 IMMUNOLOGY
Ellen D. Kaan , Tammo E. Brunekreef , Julia Drylewicz , Lucas L. van den Hoogen , Maarten van der Linden , Helen L. Leavis , Jacob M. van Laar , Michiel van der Vlist , Henny G. Otten , Maarten Limper
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引用次数: 0

摘要

目的系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特点是疾病症状多样,临床病程难以预测。为了改善治疗效果,根据系统性红斑狼疮患者常见的免疫学表现(如自身抗体、I型干扰素(IFN)特征和中性粒细胞胞外捕获物(NET)释放)进行分层可能会有所帮助。据推测,这些免疫现象之间存在关联,因为NET的释放会诱导IFN的产生,而IFN会通过B细胞活化诱导自身抗体的形成。我们对 25 名系统性红斑狼疮患者的 57 种系统性红斑狼疮相关自身抗体进行了主成分分析(PCA)和分层聚类。我们将每种自身抗体与 IFN 标志和 NET 诱导能力相关联。结果我们观察到两个不同的群组:一个群组主要包含具有高 IFN 标志的患者。这个群组的患者通常伴有皮肤狼疮,抗dsDNA浓度较高。另一个群组则混合了高IFN和低IFN特征的患者。具有高和低NET诱导能力的患者在两个群组之间分布相当。群组间的差异主要由针对组蛋白、RibP2、RibP0、EphB2、RibP1、PCNA、dsDNA和核小体的抗体驱动。此外,我们还发现在有IFN特征的患者中,针对EphB2、RibP1和RNP70的自身抗体浓度呈上升趋势。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。我们没有发现自身抗体与NET诱导能力之间存在正相关。我们的研究进一步加强了RNA结合自身抗体与IFN特征之间相关性的证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus

Objective

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.

Methods

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.

Results

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).

Conclusion

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.

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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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