Idiopathic inflammatory myopathies lack neutralising autoantibodies to type- I, II and III interferons.

IF 4.7 2区 医学 Q1 RHEUMATOLOGY
Anish Behere, Hedvig Mildner, Irene Peralta Garcia, César Pérez Bucio, Ingrid Lundberg, Begum Horuluoglu, Nils Landegren
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Abstract

Objective: To determine whether autoantibodies against interferons are present and play a role in disease modulation in idiopathic inflammatory myopathies (IIMs).

Methods: We screened for autoantibodies against a large number of interferons (IFNs) and other cytokines in a cross-sectional observational cohort of Swedish patients with anti-synthetase syndrome (n=51) and dermatomyositis (n=48), matched together with blood donors (n=100) from general population, using both planar and suspension-based multiplex assays. A single patient with autoimmune polyendocrine syndrome, type-1 (APS-1), known to harbour autoantibodies that neutralise type-I interferons, was included as a reference biological positive. The functional ability of autoantibodies to neutralise type-I interferons was tested in vitro, using an IFN-α/β responsive cell reporter assay.

Result: The initial screening of plasma samples indicated a repertoire of autoantibodies in IIM patients against a number of common myositis-specific and myositis-associated antigens. On screening for autoantibodies against type-I, II or III interferons, we did not find any evidence of anti-IFN autoantibodies being present in any of the IIM patient subgroups or the blood donors from general population. Additionally, none of the tested plasma samples, except the APS-1, exhibited neutralisation of physiological concentration IFN-α2, further confirming a complete lack of functional autoantibodies against IFN-α subtypes in this cohort.

Conclusions: We did not detect neutralising autoantibodies against IFN-α and autoantibodies against other types of IFNs in a Swedish cohort of IIM patients. These findings contrast with the presence of autoantibodies against type-I IFNs in other systemic autoimmune diseases, such as systemic lupus erythematosus, characterised by type-I IFN overactivation.

特发性炎性肌病缺乏对I型、II型和III型干扰素的中和性自身抗体。
目的:确定特发性炎性肌病(IIMs)中是否存在抗干扰素的自身抗体并在疾病调节中发挥作用。方法:我们在瑞典抗合成酶综合征(n=51)和皮肌炎(n=48)患者的横断面观察队列中筛选针对大量干扰素(ifn)和其他细胞因子的自身抗体,并与来自一般人群的献血者(n=100)相匹配,使用平面和基于悬液的多重检测。1例自身免疫性多内分泌综合征1型(APS-1)患者被纳入参考生物学阳性,该患者已知含有中和1型干扰素的自身抗体。使用IFN-α/β反应性细胞报告试验,在体外测试了自身抗体中和i型干扰素的功能能力。结果:血浆样本的初步筛选表明,IIM患者对许多常见的肌炎特异性和肌炎相关抗原具有一系列自身抗体。在筛选针对i型、II型或III型干扰素的自身抗体时,我们没有发现任何证据表明在任何IIM患者亚组或来自一般人群的献血者中存在抗ifn自身抗体。此外,除了APS-1外,所有测试的血浆样本都没有表现出生理浓度IFN-α2的中和,进一步证实了该队列中完全缺乏针对IFN-α亚型的功能性自身抗体。结论:我们在瑞典IIM患者队列中未检测到针对IFN-α的中和性自身抗体和针对其他类型IFN的自身抗体。这些发现与其他系统性自身免疫性疾病(如系统性红斑狼疮)中针对i型IFN的自身抗体的存在形成对比,系统性红斑狼疮以i型IFN过度激活为特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
RMD Open
RMD Open RHEUMATOLOGY-
CiteScore
7.30
自引率
6.50%
发文量
205
审稿时长
14 weeks
期刊介绍: RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
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