Wen Jingping, Zhou Mianjing, Lai Yimei, Zhuang Lili, Shi Jia, Lin Zhangmei, Chen Binfeng, Li Mengyuan, Yang Niansheng, Wang Shuyi
Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Clin Rheumatol. 2025 Jan;44(1):327-340. doi: 10.1007/s10067-024-07227-5. Epub 2024 Nov 23.
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders with uncertain pathogenesis. Interferon (IFN)-λ has recently been described as an important mediator of immune responses. The main purpose of this study is to find out whether IFN-λ is involved in IIM.
The published RNA-seq data of dermatomyositis (DM) muscle and IIM double negative (DN) B cells were analyzed. Serum IFN-λ1, IFN-λ2, and IFN-λ3 levels of 59 IIM patients and 29 healthy persons were determined by enzyme-linked immunosorbent assay (ELISA). The proportion of DN B cells and subsets as well as phosphorylated STAT1 (p-STAT1) levels in peripheral B cells was measured by flow cytometry. Ex vivo induction of double negative 2 (DN2) B cells were performed for validation.
Type III IFN signaling pathway was enriched in muscle tissue from DM patients. Serum IFN-λ1, IFN-λ2, and IFN-λ3 levels were significantly higher in the IIM patients, especially patients with interstitial lung disease (ILD) and skin manifestations. Moreover, serum IFN-λ1 level was positively correlated with the disease activity. In addition, IIM patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies exhibited higher serum IFN-λ1, IFN-λ2, and IFN-λ3 levels. The frequency of DN2 B cells were elevated in IIM patients' blood. Interestingly, the type III IFN signaling pathway was enriched in circulating DN2 B cells from IIM patients, which could induce T-betCD19 DN2 B cell differentiation ex vivo.
IFN-λ may participate in the pathogenesis of IIM by acting on DN2 B cells and serve as a disease biomarker for IIM patients. Key Points • Type III IFN signaling pathway is enriched in the involved muscles of DM patients. • Serum IFN-λ in IIM patients is correlated with disease activity and is higher in patients with ILD, skin lesions, and positive anti-MDA5 antibodies. • DN2 B cells with enriched type III IFN signaling pathway are accumulated in the peripheral blood of IIM patients.
特发性炎症性肌病（IIM）是一组发病机制不明的异质性自身免疫性疾病。干扰素（IFN）-λ最近被描述为免疫反应的重要介质。本研究的主要目的是探究IFN-λ是否参与IIM。
分析已发表的皮肌炎（DM）肌肉和IIM双阴性（DN）B细胞的RNA测序数据。采用酶联免疫吸附测定（ELISA）法测定59例IIM患者和29例健康人的血清IFN-λ1、IFN-λ2和IFN-λ3水平。通过流式细胞术检测外周血B细胞中DN B细胞及其亚群的比例以及磷酸化信号转导和转录激活因子1（p-STAT1）水平。进行体外双阴性2（DN2）B细胞诱导以进行验证。
III型IFN信号通路在DM患者的肌肉组织中富集。IIM患者血清IFN-λ1、IFN-λ2和IFN-λ3水平显著升高，尤其是合并间质性肺疾病（ILD）和有皮肤表现的患者。此外，血清IFN-λ1水平与疾病活动度呈正相关。另外，抗黑色素瘤分化相关基因5（anti-MDA5）抗体阳性的IIM患者血清IFN-λ1、IFN-λ2和IFN-λ3水平更高。IIM患者血液中DN2 B细胞频率升高。有趣的是，III型IFN信号通路在IIM患者循环DN2 B细胞中富集，可在体外诱导T-bet⁺CD19⁻ DN2 B细胞分化。
IFN-λ可能通过作用于DN2 B细胞参与IIM的发病机制，并可作为IIM患者的疾病生物标志物。要点 • III型IFN信号通路在DM患者受累肌肉中富集。• IIM患者血清IFN-λ与疾病活动度相关，在合并ILD、有皮肤病变及anti-MDA5抗体阳性的患者中更高。• III型IFN信号通路富集的DN2 B细胞在IIM患者外周血中积聚。
