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Sci Rep. 2019 Mar 14;9(1):4530. doi: 10.1038/s41598-019-40900-3.

Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations.

Author information

1
Centre de Recherche du CHU de Québec - Université Laval, Département de microbiologie et immunologie, Faculté de Médecine de l'Université Laval, Québec, Qc, Canada.
2
Division de Rhumatologie, Département de Médecine, CHU de Québec - Université Laval, Québec, Qc, Canada.
3
Département de mathématiques et statistique, Université Laval, Québec, Qc, Canada.
4
Women's College Hospital and University of Toronto, Toronto, ON, Canada.
5
Immunology and Histocompatibility Laboratory, Department of Medical Biology CHU de Québec - Université Laval; Department of Microbiology, Infectious Diseases and Immunology, Université Laval, Québec, Qc, Canada.
6
Axe maladies infectieuses et inflammatoires, Centre de recherche du CHU de Québec - Université Laval, Québec, Qc, Canada.
7
Axe Neurosciences, Centre de Recherche du CHU de Québec - Université Laval, Québec, Qc, Canada.
8
Axe Reproduction, Santé de la mère et de l'enfant, Centre de recherche du CHU de Québec - Université Laval, Québec, Qc, Canada.
9
Centre de recherche du CHU de Montréal, Montréal Québec, Québec, Qc, Canada.
10
Division of Rheumatology, Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Qc, H4A 3J1, Canada.
11
Division de Rhumatologie, Département de Médecine, CHU de Québec - Université Laval, Québec, Qc, Canada. paul.fortin@crchudequebec.ulaval.ca.
12
Axe maladies infectieuses et inflammatoires, Centre de recherche du CHU de Québec - Université Laval, Québec, Qc, Canada. paul.fortin@crchudequebec.ulaval.ca.
13
Centre de Recherche du CHU de Québec - Université Laval, Département de microbiologie et immunologie, Faculté de Médecine de l'Université Laval, Québec, Qc, Canada. eric.boilard@crchudequebec.ulaval.ca.
14
Axe maladies infectieuses et inflammatoires, Centre de recherche du CHU de Québec - Université Laval, Québec, Qc, Canada. eric.boilard@crchudequebec.ulaval.ca.

Abstract

Mitochondria are organelles that govern energy supply and control cell death. Mitochondria also express bacterial features, such as the presence of inner membrane cardiolipin and a circular genome rich in hypomethylated CpG motifs. While mitochondrial extrusion by damaged organs or activated cells is thought to trigger innate immunity, it is unclear whether extracellular mitochondria also stimulate an adaptive immune response. We describe the development of novel assays to detect autoantibodies specific to two distinct components of the mitochondrion: the mitochondrial outer membrane and mitochondrial DNA. Antibodies to these two mitochondrial constituents were increased in both human and murine systemic lupus erythematosus (SLE), compared to controls, and were present at higher levels than in patients with antiphospholipid syndrome or primary biliary cirrhosis. In both bi- and multi-variate regression models, antibodies to mitochondrial DNA, but not whole mitochondria, were associated with increased anti-dsDNA antibodies and lupus nephritis. This study describes new and optimized methods for the assessment of anti-mitochondrial antibodies, and demonstrates their presence in both human and murine SLE. These findings suggest that different mitochondrial components are immunogenic in SLE, and support the concept that extracellular mitochondria may provide an important source of circulating autoantigens in SLE.

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