Journal article
Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality
Annals of the rheumatic diseases, v 85(4)
12 Dec 2025
PMID: 41390302
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Systemic lupus erythematosus (SLE) remains a deadly disease, yet our ability to predict adverse outcomes is poor. Mitochondria are organelles recognised by the immune system when released from cells, and antimitochondrial antibodies (AMA) can be detected in people with SLE. We assessed AMA as markers of nephritis, arterial vascular events (AVE), and other outcomes including mortality.
We studied sera and data from 1114 participants of the Systemic Lupus International Collaborating Clinics inception cohort. We measured antiwhole mitochondria (AwMA), antimitochondrial DNA (AmtDNA), and antimitochondrial RNA (AmtRNA) antibodies by direct Enzyme-Linked ImmunoSorbent Assays (ELISAs). Separate multivariable Cox proportional hazards regression models estimated associations of either baseline or most recent measures of AMA with the outcomes, adjusted for biological sex, age, medications, and other clinical factors. Interactions of AMA with biological sex were tested for each outcome.
All AMA titres were elevated in SLE vs healthy individuals. Higher AMA levels were associated with a higher hazard of nephritis, with the strongest associations for most recent AmtDNA (adjusted hazard ratio [aHR] =1.61 for increase of 1 SD, 95% CI 1.43-1.82) and AmtRNA (aHR =1.59, 1.46-1.73). Higher baseline AwMA levels predicted early mortality (aHR =1.19, 1.02-1.40). Most recent AmtDNA (aHR =1.68, 1.28-2.19) was associated with higher mortality throughout the follow-up. For AVE, the impact of higher AmtRNA was stronger in females.
Baseline and most recent assessments of AMA levels may help identify individuals at higher risk of severe outcomes in SLE, including mortality. Integrating AMA into precision medicine strategies will allow deeper exploration of lupus heterogeneity.
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Details
- Title
- Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality
- Creators
- Yann L C BeckerÉric BoilardEmmanuelle Rollet-LabelleChristian Lood - University of WashingtonAnne-Sophie Julien - Université LavalMichal Abrahamowicz - McGill UniversityIsabelle AllaeysMay Choi - University of CalgaryJoannie Leclerc - Université LavalTania LévesqueMurray Urowitz - Schroeder Arthritis InstituteJohn G Hanly - Dalhousie UniversityCaroline Gordon - University of BirminghamSang-Cheol Bae - Hanyang University Seoul HospitalJuanita Romero-DiazJorge Sanchez-GuerreroAnn E Clarke - University of CalgarySasha BernatskyDaniel Wallace - Cedars-Sinai Medical CenterDavid Isenberg - University College LondonAnisur Rahman - University College LondonJoan Merrill - Oklahoma Medical Research FoundationDafna D Gladman - Schroeder Arthritis InstituteIan N BruceMichelle Petri - Johns Hopkins University School of MedicineEllen Ginzler - SUNY Downstate Health Sciences UniversityMary Anne Dooley - Raleigh Neurology AssociatesRosalind Ramsey-Goldman - Northwestern UniversitySusan Manzi - Allegheny Health NetworkAndreas Jönsen - Skåne University HospitalGraciela S Alarcόn - University of Alabama at BirminghamRonald van Vollenhoven - Amsterdam University Medical CentersCynthia Aranow - Feinstein Institutes for Medical Research, Manhasset, NY, USAGuillermo Ruiz-Irastorza - Biobizkaia Health Research Institute, UPV/EHU, Barakaldo, País Vasco, SpainSam Lim - Emory UniversityMurat Inanc - Istanbul UniversityKenneth Kalunian - University of California San DiegoSoren Jacobsen - RigshospitaletChristine Peschken - University of ManitobaDiane Kamen - Medical University of South CarolinaAnca Askanase - Columbia University Irving Medical CenterJill Buyon - New York University Grossman School of Medicine, New York, NY, USAPaul R Fortin
- Publication Details
- Annals of the rheumatic diseases, v 85(4)
- Publisher
- ELSEVIER; AMSTERDAM
- Number of pages
- 10
- Grant note
- CIHR CIB grant: PJT-162353 Fonds de Recherche du Quebec en Sante (FRQS) NIH: 1 R21 AR077565, 1 R21 AR079542, 1 R01 IL158606 Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education: NRF-2021R1A6A1A03038899 FRQS CIHR: MOP-57752, MOP-86526, MOP-88526
This study was supported by CIHR CIB grant PJT-162353. YLCB is supported by fellowships from the Fonds de Recherche du Quebec en Sante (FRQS) and from the ARThrite Research Center. CL is supported by awards from the NIH (1 R21 AR077565, 1 R21 AR079542, and 1 R01 IL158606). S-CB is supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1A6A1A03038899). EB is supported by a senior award from the FRQS. The SLICC neuro-psychiatric study led by JGH was supported by CIHR grants MOP-57752, MOP-86526, and MOP-88526.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:001761108800001
- Scopus ID
- 2-s2.0-105028840953
- Other Identifier
- 991022146942304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology