TOPLINE:

Higher levels of antimitochondrial antibodies in patients with systemic lupus erythematosus (SLE) were associated with an increased risk for severe outcomes such as death and arterial vascular events. Recent antimitochondrial DNA levels were linked to mortality throughout the follow-up period.

METHODOLOGY:

• Researchers assessed antimitochondrial antibodies in 1114 patients (mean age, 35.4 years; 89% female) with SLE from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, who were recruited from 1999 to 2011, with up to 21 years of follow-up.
• Healthy control individuals, matched for age and sex (n = 127; mean age, 35.2 years; 82% female), were recruited from two centers to define antimitochondrial antibody levels in a healthy population.
• Three new tests were developed to detect antimitochondrial antibodies — targeting the outer membrane of the mitochondria (anti-whole mitochondria antibody), mitochondrial DNA, and mitochondrial RNA.
• Sera and clinical data (including disease activity measures) were collected at baseline and annually, with repeated antibody measurements over time. Antimitochondrial antibody levels were measured using direct enzyme-linked immunosorbent assays.
• Key clinical endpoints recorded at annual visits included death, new-onset nephritis, incident arterial vascular events, neuropsychiatric lupus, and the SLICC/American College of Rheumatology Damage Index. Arterial vascular events were defined as myocardial infarction, angina, stroke, transient ischemic attack, or other cardiac events.

TAKEAWAY:

• During the 9-year median follow-up period, 56 patients died, 120 developed nephritis, 76 experienced arterial vascular events, 452 developed new damage, and 91 developed neuropsychiatric lupus.
• Baseline anti-whole mitochondria antibody levels were associated with early mortality in SLE (adjusted hazard ratio [aHR] per 1-SD increase, 1.19; 95% CI, 1.02-1.40). Moreover, over the follow-up period, higher most recent levels of antimitochondrial DNA were linked to greater mortality (aHR, 1.68; 95% CI, 1.28-2.19).
• Higher baseline levels of antimitochondrial DNA and RNA were significantly associated with nephritis (aHR, 1.42; 95% CI, 1.24-1.63 and aHR, 1.45; 95% CI, 1.31-1.61, respectively), with similar associations noted for recent DNA and RNA levels.
• Higher recent levels of antimitochondrial DNA were linked to an increased risk for arterial vascular events (aHR, 1.22; 95% CI, 1.009-1.47). Higher recent levels of antimitochondrial RNA were associated with a higher risk for arterial vascular events in women (aHR, 1.34; 95% CI, 1.07-1.67), whereas higher baseline levels were associated with a lower risk for arterial vascular events in men (aHR, 0.56; 95% CI, 0.34-0.93).

IN PRACTICE:

“Detection of elevated [anti-whole mitochondria antibody] at the time of diagnosis, or persistently elevated [antimitochondrial DNA] or [antimitochondrial RNA] during disease course, should prompt careful initial assessment and cautious follow-up. Integrating antibodies directed to the mitochondrial organelle into precision medicine strategies will allow deeper exploration of lupus heterogeneity,” the authors of the study concluded.

SOURCE:

The study was led by Yann L.C. Becker, PhD, who conducted the research while a postdoctoral fellow at the ARThrite Research Centre, Université Laval, Quebec City, Quebec, Canada. It was published online on December 12, 2025, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The study did not evaluate how useful antimitochondrial antibodies are when used in combination with other known biomarkers. The number of male participants was limited.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Some authors reported being supported by fellowships from the Fonds de Recherche du Québec en Santé and the ARThrite Research Centre, awards from the National Institutes of Health, or the Basic Science Research Program through the National Research Foundation of Korea. Three authors reported filing a provisional patent for kits to detect antimitochondrial antibodies in SLE.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.