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Open Access Highly Accessed Open Badges Research article

Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes

Tanya R Da Sylva1*, Alison Connor2, Yvonne Mburu1, Edward Keystone3 and Gillian E Wu1

Author Affiliations

1 Department of Biology, York University, Toronto, Ontario, Canada

2 The Wellesley Toronto Arthritis and Immune Disorder Research Centre, University Health Network, Toronto, Ontario, Canada

3 Department of Medicine, University of Toronto, Mount Sinai Hospital, Toronto, Ontario, Canada

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Arthritis Research & Therapy 2005, 7:R844-R851  doi:10.1186/ar1752

Published: 28 April 2005


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.