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系统性红斑狼疮患者视神经脊髓炎病程中自身抗体和细胞因子反应的变化:一项初步研究。

Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study.

作者信息

Kovacs Katalin T, Kalluri Sudhakar Reddy, Boza-Serrano Antonio, Deierborg Tomas, Csepany Tunde, Simo Magdolna, Rokusz Laszlo, Miseta Attila, Alcaraz Nicolas, Czirjak Laszlo, Berki Timea, Molnar Tihamer, Hemmer Bernhard, Illes Zsolt

机构信息

Department of Rheumatology and Immunology, University of Pecs, Hungary.

Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Germany.

出版信息

Mult Scler. 2016 Aug;22(9):1192-201. doi: 10.1177/1352458515613165. Epub 2015 Oct 29.

Abstract

BACKGROUND

Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies.

OBJECTIVE

To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute.

METHODS

In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission.

RESULTS

AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05).

CONCLUSIONS

AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.

摘要

背景

视神经脊髓炎(NMO)-系统性红斑狼疮(SLE)关联是一种以多种自身抗体为特征的罕见病症。

目的

研究在NMO演变过程中,抗水通道蛋白4(AQP4)反应是否是多克隆B细胞活化的一部分,以及T细胞反应是否起作用。

方法

在6例于SLE病程中发生NMO的患者的19份样本中,我们检测了AQP4-IgG1和IgM与以下各项的相关性:(i)抗髓鞘少突胶质细胞糖蛋白(MOG)IgG和IgM,(ii)抗核、抗核小体和抗双链DNA(dsDNA)IgG抗体,(iii)血清中的细胞因子和趋化因子,以及(iv)与NMO复发/缓解的纵向关系。

结果

AQP4-IgG1在首次NMO复发前1 - 2 - 5年就已存在。在复发期间,AQP4-IgG1、抗核抗体(ANA)、抗dsDNA和抗核小体抗体升高。未检测到抗MOG IgG/IgM和AQP4-IgM抗体。AQP4-IgG1抗体与抗核小体浓度、干扰素-γ(IFN-γ)、干扰素-γ诱导的CCL10/IP-10和CCL17/TARC相关(p值分别<0.05)。CCL17/TARC与抗核小体和抗dsDNA水平相关(p值分别<0.05)。与健康受试者相比,NMO/SLE患者中IFN-γ和CCL17/TARC的浓度更高(p<0.05)。

结论

在SLE患者首次发生NMO攻击前数年,血清中就存在AQP4-IgG1抗体;抗AQP4升高是NMO复发期间多克隆B细胞反应的一部分;尽管血清中有多种自身抗体,但未检测到MOG抗体;在NMO/SLE中,Th1反应伴随自身抗体反应。

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