Wu Yuanhui, Luo Jiao, Duan Lihua
Jiangxi Province Key Laboratory of Immunity and Inflammation, Jiangxi Provincial People's Hospital, Nanchang, China.
Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
Front Immunol. 2024 Aug 30;15:1439807. doi: 10.3389/fimmu.2024.1439807. eCollection 2024.
Idiopathic inflammatory myopathies (IIMs) encompass a spectrum of autoimmune diseases characterized by muscle inflammation and systemic involvement. This review aimed to synthesize current evidence on the clinical significance and pathogenic mechanisms underlying autoantibodies associated with IIMs. Autoantibodies targeting aminoacyl-tRNA synthetases (ARS) play a pivotal role in antisynthetase syndrome (ASS), highlighting associations with interstitial lung disease (ILD) and distinctive clinical features. Anti-Mi-2 antibodies in dermatomyositis (DM) are hallmarked by characteristic cutaneous manifestations and favorable prognostic outcomes. Conversely, anti-TIF1 antibodies are correlated with DM and a higher risk of malignancies, implicating CD8 T cells in its pathogenesis. Anti-MDA5 antibodies signify clinically amyopathic DM (CADM) with severe ILD, linked to dysregulated neutrophil extracellular trap (NET) formation. In immune-mediated necrotizing myopathies (IMNMs), anti-SRP and anti-HMGCR antibodies induce complement-mediated myopathy, typically following statin exposure. Additionally, anti-TRIM72 antibodies emerge as potential diagnostic markers in IIMs. Anti-cN1A autoantibodies are linked to inclusion body myositis (IBM) and play a decisive role in muscle protein degradation. Meanwhile, anti-FHL1 autoantibodies are associated with severe disease manifestations and muscle damage, as established in experimental models. Anti-eIF3 autoantibodies, recently identified in polymyositis (PM) patients, are rarely detected (<1%) and associated with a favorable prognosis. Elucidating these autoantibodies is anticipated to not only assist in early diagnosis and disease stratification but also inform targeted therapeutic interventions, emphasizing the intricate interplay between autoimmunity, cellular dysfunction, and clinical outcomes in IIMs.
特发性炎性肌病（IIMs）是一系列以肌肉炎症和全身受累为特征的自身免疫性疾病。本综述旨在综合目前关于与IIMs相关自身抗体的临床意义和致病机制的证据。靶向氨酰-tRNA合成酶（ARS）的自身抗体在抗合成酶综合征（ASS）中起关键作用，突出了其与间质性肺病（ILD）的关联以及独特的临床特征。皮肌炎（DM）中的抗Mi-2抗体以特征性皮肤表现和良好的预后为特点。相反，抗TIF1抗体与DM及更高的恶性肿瘤风险相关，提示CD8 T细胞参与其发病机制。抗MDA5抗体表明临床上无肌病性DM（CADM）伴严重ILD，与中性粒细胞胞外诱捕网（NET）形成失调有关。在免疫介导的坏死性肌病（IMNMs）中，抗SRP和抗HMGCR抗体诱导补体介导的肌病，通常在他汀类药物暴露后发生。此外，抗TRIM72抗体成为IIMs中的潜在诊断标志物。抗cN1A自身抗体与包涵体肌炎（IBM）相关，并在肌肉蛋白降解中起决定性作用。同时，抗FHL1自身抗体与严重疾病表现和肌肉损伤相关，这在实验模型中已得到证实。最近在多发性肌炎（PM）患者中发现的抗eIF3自身抗体很少被检测到（<1%），且与良好预后相关。阐明这些自身抗体不仅有望有助于早期诊断和疾病分层，还能为靶向治疗干预提供依据，强调了IIMs中自身免疫、细胞功能障碍和临床结果之间的复杂相互作用。
