Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes.
Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes.
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DOI：
10.1186/ar1752
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发表时间：
2005
影响因子：
4.9
通讯作者：
Wu GE
中科院分区：
文献类型：
--
作者：
Da Sylva TR;Connor A;Mburu Y;Keystone E;Wu GE
体细胞突变在许多疾病的发病机制中发挥作用，尤其是癌症。在这里，我们提供的数据支持线粒体体细胞突变在自身免疫性疾病类风湿性关节炎(RA)中的作用。RA是一种复杂的、多因素的疾病，具有许多易感性特征，包括主要组织相容性复合体(MHC)型和关节早期细菌感染。MHC显示的线粒体多肽的体细胞突变可能被认为是非自我的，进一步促进了RA关节的破坏性免疫渗透。因为许多细菌蛋白都有线粒体同源物，如果这些改变的多肽模仿细菌同源物，免疫系统可能会对这些改变的多肽产生反应。此外，体细胞突变可能影响细胞功能，帮助获得类风湿关节炎滑膜细胞的转化特性。为了验证线粒体DNA(MtDNA)突变与类风湿关节炎(RA)相关的假说，我们以骨关节炎(OA)患者滑膜细胞线粒体中线粒体NADH脱氢酶1(复合体I-NADH脱氢酶亚基1)的MT-ND1基因为研究对象，对其进行了研究。我们确定了两组患者潜在表位区域的突变负荷和氨基酸变化。RA滑膜细胞mtDNA的突变数量大约是OA组的两倍。此外，这些变化中的一些已经导致了潜在的非自身MHC多肽表位。这些结果为线粒体DNA的体细胞突变在RA中的新作用提供了证据，并预测了在其他疾病中的作用。
Somatic mutations have a role in the pathogenesis of a number of diseases, particularly cancers. Here we present data supporting a role of mitochondrial somatic mutations in an autoimmune disease, rheumatoid arthritis (RA). RA is a complex, multifactorial disease with a number of predisposition traits, including major histocompatibility complex (MHC) type and early bacterial infection in the joint. Somatic mutations in mitochondrial peptides displayed by MHCs may be recognized as non-self, furthering the destructive immune infiltration of the RA joint. Because many bacterial proteins have mitochondrial homologues, the immune system may be primed against these altered peptides if they mimic bacterial homologues. In addition, somatic mutations may be influencing cellular function, aiding in the acquirement of transformed properties of RA synoviocytes. To test the hypothesis that mutations in mitochondrial DNA (mtDNA) are associated with RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH dehydrogenase 1 (subunit one of complex I – NADH dehydrogenase) of synoviocyte mitochondria from RA patients, using tissue from osteoarthritis (OA) patients for controls. We identified the mutational burden and amino acid changes in potential epitope regions in the two patient groups. RA synoviocyte mtDNA had about twice the number of mutations as the OA group. Furthermore, some of these changes had resulted in potential non-self MHC peptide epitopes. These results provide evidence for a new role for somatic mutations in mtDNA in RA and predict a role in other diseases.
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影响因子：
4.8
作者：
Harris, RA;BowkerKinley, MM;Popov, KM
通讯作者：
Popov, KM
DOI：
10.1073/pnas.152333199
发表时间：
2002-07-23
影响因子：
11.1
作者：
Yamanishi, Y;Boyle, DL;Firestein, GS
通讯作者：
Firestein, GS
影响因子：
14.9
作者：
Taylor, RW;Taylor, GA;Turnbull, DM
通讯作者：
Turnbull, DM
影响因子：
14.9
作者：
Guan, PP;Doytchinova, IA;Flower, DR
通讯作者：
Flower, DR
影响因子：
15.9
作者：
Pitkanen, S;Robinson, BH
通讯作者：
Robinson, BH