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The binding of SLE autoantibodies to mitochondria.
Clinical Immunology ( IF 8.6 ) Pub Date : 2020-01-24 , DOI: 10.1016/j.clim.2020.108349
David S Pisetsky 1 , Diane M Spencer 2 , Fariborz Mobarrez 3 , Enrico Fuzzi 4 , Iva Gunnarsson 5 , Elisabet Svenungsson 5
Affiliation  

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes. Because these complexes contain mitochondrial components, we assessed the presence of antibodies to whole mitochondria (wMITO) using an ELISA in which mitochondria from mouse liver are bound to microtiter plates pre-coated with poly-l-lysine. Studies with this ELISA demonstrated that SLE plasmas contain abundant anti-wMITO activity. While digestion with DNase 1 did not affect anti-wMITO activity, adsorption of plasma on DNA affinity columns could reduce binding activity. Assay for anti-mitochondrial antibodies (AMA) by immunofluorescence and an ELISA with the M2 antigen (2-oxo-acid dehydrogenase protein complex) showed a low frequency of positivity, indicating that AMA and anti-wMITO are distinct specificities. In the study of 204 patients with SLE, the levels of anti-wMITO were higher in active SLE and correlated with levels of anti-DNA. These findings suggest that anti-wMITO can form immune complexes with mitochondria which may drive pathogenesis.

中文翻译:

SLE 自身抗体与线粒体的结合。

系统性红斑狼疮(SLE)是一种以免疫复合物为特征的典型自身免疫性疾病。由于这些复合物含有线粒体成分,我们使用 ELISA 评估了全线粒体抗体 (wMITO) 的存在,其中来自小鼠肝脏的线粒体与预先涂有聚-L-赖氨酸的微量滴定板结合。该 ELISA 研究表明,SLE 血浆含有丰富的抗 wMITO 活性。虽然用 DNase 1 消化不会影响抗 wMITO 活性,但血浆在 DNA 亲和柱上的吸附可能会降低结合活性。通过免疫荧光和 M2 抗原(2-含氧酸脱氢酶蛋白复合物)ELISA 进行的抗线粒体抗体 (AMA) 检测显示阳性频率较低,表明 AMA 和抗 wMITO 具有不同的特异性。在对 204 名 SLE 患者进行的研究中,活动性 SLE 患者的抗 wMITO 水平较高,并且与抗 DNA 水平相关。这些发现表明,抗 wMITO 可以与线粒体形成免疫复合物,这可能驱动发病机制。
更新日期:2020-01-24
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