关键词: HRS (histidyl-tRNA synthetase) Ro52 Ro60 antibody myositis

Mesh : Animals Humans Ribonucleoproteins / immunology Myositis / immunology Female Mice Male Middle Aged Antibodies, Antinuclear / immunology blood Autoantibodies / blood immunology Aged Adult Histidine-tRNA Ligase / immunology Disease Models, Animal Autoantigens / immunology RNA, Small Cytoplasmic

来  源:   DOI:10.3389/fimmu.2024.1399451   PDF(Pubmed)

Abstract:
UNASSIGNED: Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently associated with various myositis-specific autoantibodies (MSAs)-including anti-tRNA synthetase antibodies-and that the coexistence of MSAs and anti-Ro52 antibodies may portend worse clinical outcomes. Although not well-described in the setting of myositis, work from our animal model of HRS (histidyl-tRNA synthetase)-induced myositis suggests that anti-Ro60 antibodies may also be linked to specific MSAs such as anti-HRS/Jo-1. We therefore aimed to demonstrate the prevalence and clinical characteristics of Ro52 and Ro60 antibody positivity in patients possessing Jo-1 antibodies.
UNASSIGNED: To establish the immunological link between anti-synthetase, anti-Ro52, and anti-Ro60 antibodies, we evaluated the relative titers of these antibodies in blood and bronchoalveolar lavage fluid (BALF) of mice following immunization with HRS/Jo-1. In parallel, we used ELISA-based approaches to assess sera from 177 anti-Jo1 antibody-positive patients for the presence of anti-Ro52 and/or anti-Ro60 antibodies. We then determined statistical associations between co-existing anti-Jo-1, anti-Ro52, and/or anti-Ro60 antibodies and clinical manifestations associated with the anti-synthetase syndrome.
UNASSIGNED: Mice immunized with HRS had higher levels of anti-Ro52 and anti-Ro60 antibodies in serum and BALF than PBS-immunized mice. In 177 anti-Jo-1 antibody-positive patients, the prevalence of anti-Ro52 and anti-Ro60 antibodies was 36% and 15%, respectively. The frequency of dry eye/dry mouth, interstitial pneumonia, and pulmonary events over time differed between patients with various combinations of anti-Ro52 and anti-Ro60 antibodies. While anti-Ro52 antibodies generally correlated with statistically significant increases in each of these clinical manifestations, the presence of Ro60 antibodies alone was associated with decreased frequency of ILD.
UNASSIGNED: Anti-Ro52 and/or anti-Ro60 antibodies are often co-expressed with anti-Jo1 antibodies, defining clinical subsets with different disease course/outcomes.
摘要:
抗SSA抗体靶向两种不相关的蛋白质,Ro52(E3连接酶)和Ro60(RNA结合蛋白)。先前的研究表明,抗Ro52抗体通常与各种肌炎特异性自身抗体(MSA)(包括抗tRNA合成酶抗体)相关,并且MSA和抗Ro52抗体的共存可能预示着更差的临床结果。虽然在肌炎的背景下没有很好的描述,我们对HRS(组氨酸tRNA合成酶)诱导肌炎动物模型的研究表明,抗Ro60抗体也可能与特定的MSA如抗HRS/Jo-1相关.因此,我们旨在证明具有Jo-1抗体的患者中Ro52和Ro60抗体阳性的患病率和临床特征。
为了建立抗合成酶之间的免疫学联系,抗Ro52和抗Ro60抗体,我们评估了HRS/Jo-1免疫后小鼠血液和支气管肺泡灌洗液(BALF)中这些抗体的相对滴度.并行,我们使用基于ELISA的方法评估了177例抗Jo1抗体阳性患者的血清中是否存在抗Ro52和/或抗Ro60抗体.然后,我们确定了共存的抗Jo-1,抗Ro52和/或抗Ro60抗体与与抗合成酶综合征相关的临床表现之间的统计关联。
用HRS免疫的小鼠比PBS免疫的小鼠在血清和BALF中具有更高水平的抗Ro52和抗Ro60抗体。在177名抗Jo-1抗体阳性患者中,抗Ro52和抗Ro60抗体的患病率分别为36%和15%,分别。干眼/口干的频率,间质性肺炎,抗Ro52和抗Ro60抗体各种组合的患者之间的肺事件随时间的变化不同。虽然抗Ro52抗体通常与这些临床表现中的每一个的统计学显著增加相关,单独存在Ro60抗体与ILD发生频率降低相关.
抗Ro52和/或抗Ro60抗体通常与抗Jo1抗体共表达,定义具有不同病程/结局的临床子集。
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