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Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality
Journal article   Peer reviewed

Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality

Yann L C Becker, Éric Boilard, Emmanuelle Rollet-Labelle, Christian Lood, Anne-Sophie Julien, Michal Abrahamowicz, Isabelle Allaeys, May Choi, Joannie Leclerc, Tania Lévesque, …
Annals of the rheumatic diseases
12 Dec 2025
DOI: https://doi.org/10.1016/j.ard.2025.11.007
PMID: 41390302

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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