Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, United States of America; Medical Research Service, VA Medical Center, Durham, NC, United States of America.
Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, United States of America.
Clin Immunol. 2020 Mar;212:108349. doi: 10.1016/j.clim.2020.108349. Epub 2020 Jan 24.
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.
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 评估了针对完整线粒体 (wMITO) 的抗体的存在，其中将来自小鼠肝脏的线粒体结合到预先用多聚赖氨酸包被的微量滴定板上。使用该 ELISA 的研究表明，SLE 血浆中含有丰富的抗 wMITO 活性。虽然用 DNA 酶 1 消化不会影响抗 wMITO 活性，但将血浆吸附在 DNA 亲和柱上可以降低结合活性。通过免疫荧光法和针对 M2 抗原（2-氧酸脱氢酶蛋白复合物）的 ELISA 检测线粒体抗体 (AMA) 的研究显示阳性率较低，表明 AMA 和抗 wMITO 是不同的特异性。在对 204 例 SLE 患者的研究中，活动期 SLE 患者的抗 wMITO 水平较高，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，这可能推动发病机制。
