青少年特发性关节炎患者对染色质的自身抗体反应。

IF 10.9 1区 医学 Q1 RHEUMATOLOGY
Viola Pitkänen, Terhi Remes-Pakarinen, Paula Vähäsalo, Milja Möttönen, Minna-Maija Grönlund, Miika Arvonen, Mikael Knip, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Johanna Lempainen, Anna-Mari Schroderus, Liisa Kröger, Tuure Kinnunen
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引用次数: 0

摘要

目的:幼年特发性关节炎(JIA)患者经常表现出抗核抗体(ANAs),但它们识别的特异性抗原靶点以及JIA患者中是否存在其他自身抗体特异性尚不清楚。方法:对110例未经治疗的活动性JIA患者、14例不明关节炎儿童和151例年龄和性别匹配的健康儿童的血浆样本进行了多种现代临床级自身抗体分析,包括用HEp-2细胞筛选ANAs的自动间接免疫荧光和检测对个体自身抗原的反应性的特异性免疫分析。此外,利用HuProt蛋白质组芯片在5例ana阳性JIA患者和4例ana阴性健康对照的血浆样本中筛选新的自身抗体靶点。结果:在大多数(61.8%)JIA患者中检测到同质核ANA染色,表明对染色质具有反应性,但在健康对照中很少检测到(2.6%);P结论:JIA自身抗体反应性主要针对染色质,但靶向的表位可能是翻译后修饰或多分子表位,如dsDNA-核小体复合物,而不是单个天然蛋白或纯化dsDNA的表位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autoantibody Response Toward Chromatin in Patients With Juvenile Idiopathic Arthritis.

Objective: Patients with juvenile idiopathic arthritis (JIA) frequently exhibit antinuclear antibodies (ANAs), but the specific antigen target recognized by them and the presence of additional autoantibody specificities in patients with JIA remains elusive.

Methods: Plasma samples from 110 untreated patients with active JIA, as well as from 14 children with unspecified arthritis and 151 age- and sex-matched healthy children, were analyzed with multiple modern clinical-grade autoantibody assays, including automated indirect immunofluorescence to screen for ANAs with HEp-2 cells, and specific immune assays to detect reactivity to individual autoantigens. In addition, a HuProt proteome microarray was used to screen for novel autoantibody targets in plasma samples from five patients with ANA-positive JIA and four ANA-negative healthy controls.

Results: Homogeneous nuclear ANA staining, indicating reactivity toward chromatin, was detected in most (61.8%) patients with JIA but rarely in healthy controls (2.6%; P < 0.0001). No antibody reactivity to specific nuclear antigens or other autoantigens associated with connective tissue diseases was detected. However, 20% of patients with JIA harbored antibodies against double-stranded DNA (dsDNA)-nucleosome complexes (compared with 2.6% of controls, P < 0.0001). Finally, the proteome microarray revealed core histone H2A variant H2AFY, part of the nucleosome, to be the most widely recognized human protein by autoantibodies of patients with JIA.

Conclusion: Autoantibody reactivity in JIA primarily targets chromatin, but the epitopes targeted are likely either posttranslationally modified or multimolecule epitopes, such as dsDNA-nucleosome complexes, rather than epitopes on individual native proteins or purified dsDNA.

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来源期刊
Arthritis & Rheumatology
Arthritis & Rheumatology RHEUMATOLOGY-
CiteScore
20.90
自引率
3.00%
发文量
371
期刊介绍: Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.
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