组蛋白与La/SSB之间的交叉识别可能是系统性红斑狼疮患者抗DNA反应性的原因。

Cross-recognition between histones and La/SSB may account for anti-DNA reactivity in SLE patients.

作者信息

Touloupi E, Routsias J G, Tzioufas A G

机构信息

Department of Pathophysiology, School of Medicine, National University of Athens, Greece.

出版信息

Clin Exp Immunol. 2005 Oct;142(1):172-9. doi: 10.1111/j.1365-2249.2005.02892.x.

DOI:10.1111/j.1365-2249.2005.02892.x

PMID:16178873

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1809500/

Abstract

Antibodies to La/SSB are detected in sera of patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE). The vast majority of anti-La/SSB positive sera contain antibodies directed towards a linear B-cell epitope of La/SSB spanning the sequence 349-364aa (pep349-364). The aim of this study was to evaluate the fluctuation of antibody levels to major B-cell epitopes of La/SSB over time and investigate for their possible crossreactions. Sequential sera from 15 SLE and 15 pSS patients, followed from 3 to 10 years were obtained. All patients with SLE were positive for anti-Ro/SSA, anti-La/SSB and anti-dsDNA antibodies and patients with pSS were positive for anti-Ro/SSA and anti-La/SSB antibodies. Sera from 30 patients with SLE without anti-La/SSB antibodies and 30 healthy individuals served as disease and negative control respectivelly. All sera tested for the presence of anti-pep349-364 antibodies, using a specific ELISA. Specific anti-pep349-364 IgG was purified from sera of SLE patients and evaluated for cross reactivity against dsDNA and histones. In all SLE sera the levels of anti-pep349-364 antibodies varied in time and fluctuated in parallel with anti dsDNA antibodies. Anti-pep349-364 IgG purified from 7 SLE patients. Five out of 7 were found to react with calf thymus DNA in ELISA. All purified (7/7) anti-pep349-364 IgG preparations reacted with histone H1 and failed to produce a positive immunofluorescence pattern in Crithidia luciliae anti-dsDNA assay which lacks histones. Competative inhibition experiments demonstrated that histone H1 could inhibit completely the binding of anti-pep349-364 IgG to pep349-364 while pep349-364 inhibited by 70% the binding of anti-pep349-364 IgG to histone H1. These findings indicate that a subgroup of SLE patients possess cross-reacting anti-histone H1 antibodies and anti-pep349-364 antibodies, which can be faulty considered as anti-dsDNA reactivity in regular ELISA techniques.

摘要

在原发性干燥综合征（pSS）和系统性红斑狼疮（SLE）患者的血清中可检测到抗La/SSB抗体。绝大多数抗La/SSB阳性血清含有针对La/SSB线性B细胞表位的抗体，该表位跨越349 - 364氨基酸序列（肽段349 - 364）。本研究的目的是评估抗La/SSB主要B细胞表位抗体水平随时间的波动情况，并研究其可能的交叉反应。获取了15例SLE患者和15例pSS患者随访3至10年的系列血清。所有SLE患者的抗Ro/SSA、抗La/SSB和抗双链DNA（dsDNA）抗体均为阳性，pSS患者的抗Ro/SSA和抗La/SSB抗体为阳性。30例无抗La/SSB抗体的SLE患者血清和30例健康个体血清分别作为疾病对照和阴性对照。使用特异性酶联免疫吸附测定（ELISA）检测所有血清中抗肽段349 - 364抗体的存在情况。从SLE患者血清中纯化特异性抗肽段349 - 364 IgG，并评估其与dsDNA和组蛋白的交叉反应性。在所有SLE血清中，抗肽段349 - 364抗体水平随时间变化，并与抗dsDNA抗体平行波动。从7例SLE患者中纯化出抗肽段349 - 364 IgG。7例中有5例在ELISA中与小牛胸腺DNA发生反应。所有纯化的（7/7）抗肽段349 - 364 IgG制剂均与组蛋白H1发生反应，且在缺乏组蛋白的利什曼原虫抗dsDNA检测中未产生阳性免疫荧光模式。竞争性抑制实验表明，组蛋白H1可完全抑制抗肽段349 - 364 IgG与肽段349 - 364的结合，而肽段349 - 364可抑制抗肽段349 - 364 IgG与组蛋白H1结合的70%。这些发现表明，一部分SLE患者拥有交叉反应性的抗组蛋白H1抗体和抗肽段349 - 364抗体，在常规ELISA技术中可能被错误地视为抗dsDNA反应性。