A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies
A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies
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DOI：
10.1002/art.22860
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
Lundberg, Ingrid E.
中科院分区：
文献类型：
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作者：
Eloranta, Maija-Leena;Helmers, Sevim Barbasso;Lundberg, Ingrid E.
Objective.目的探讨多发性肌炎（PM）、皮肌炎（DM）和包涵体肌炎患者I型干扰素（IFN）系统的激活及其与自身抗体和器官表现的相关性。将来自30名患者和16名健康对照的血清或纯化的IgG与从坏死细胞释放的材料组合以刺激来自健康献血者的外周血单核细胞（PBMC）产生IFN α。对25例患者和7例健康对照者的肌肉活检标本进行血液树突状细胞抗原2（BDCA 2）阳性浆细胞样树突状细胞（PDCs）和IFN α/β诱导的粘液病毒耐药1（MX-1）蛋白检测。当与坏死细胞材料结合时，来自抗Jo-1或抗Ro 52/抗Ro 60自身抗体阳性的13名患者的血清诱导PBMC中的IFN α产生。此外，从抗jo-1阳性PM血清制备的IgG诱导IFN α与坏死材料，但不当后者用RNase处理。与健康个体相比，具有抗Jo-1自身抗体的PM患者肌肉组织中PDCs中BDCA-2表达增加，而DM患者毛细血管中MX-1染色增加。IFN α诱导能力与间质性肺疾病相关，而毛细血管MX-1表达与DM相关。含有抗Jo-1或抗Ro 52/抗Ro 60自身抗体和RNA的免疫复合物可作为内源性IFN α诱导剂，激活PDC中IFN α的产生。这些PDCs可能是重要的诱导肌炎，而在没有自身抗体的DM患者中，MX-1蛋白在毛细血管中的存在表明另一种细胞IFN α来源和诱导机制。因此，I型IFN系统可能在PM和DM中都是重要的，但通过不同的途径。
Objective. To investigate type I interferon (IFN) system activation and its correlation with autoantibodies and organ manifestations in polymyositis (PM), dermatomyositis (DM), and inclusion body myositis.Methods. Sera from 30 patients and 16 healthy controls, or purified IgG, were combined with material released from necrotized cells to stimulate IFN alpha production by peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Muscle biopsy specimens from 25 patients and 7 healthy controls were investigated for blood dendritic cell antigen 2 (BDCA2)-positive plasmacytoid dendritic cells (PDCs) and IFN alpha/beta-inducible myxovirus resistance 1 (MX-1) protein.Results. Sera from 13 patients who were positive for anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies induced IFN alpha production in PBMCs when combined with necrotic cell material. In addition, IgG prepared from anti-jo-1-positive PM sera induced IFN alpha with necrotic material, but not when the latter was treated with RNase. BDCA-2 expression in PDCs in muscle tissue was increased in PM patients with anti-Jo-1 autoantibodies, while MX-1 staining in capillaries was increased in DM patients, compared with healthy individuals. IFN alpha-inducing capacity correlated with interstitial lung disease, while MX-1 expression in the capillaries correlated with DM.Conclusion. Immune complexes containing antiJo-1 or anti-Ro 52/anti-Ro 60 autoantibodies and RNA may act as endogenous IFN alpha inducers that activate IFN alpha production in PDCs. These PDCs could be of importance for inducing myositis, whereas in DM patients without autoantibodies the presence of MX-1 protein in capillaries suggests another cellular IFN alpha source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.