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; Murray Urowitz; John G Hanly; Caroline Gordon; Sang-Cheol Bae; Juanita Romero-Diaz; Jorge Sanchez-Guerrero; Ann E Clarke; Sasha Bernatsky; Daniel Wallace; David Isenberg; Anisur Rahman; Joan Merrill; Dafna D Gladman; Ian N Bruce; Michelle Petri; Ellen Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jönsen; Graciela S Alarcόn; Ronald van Vollenhoven; Cynthia Aranow; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; Kenneth Kalunian; Soren Jacobsen; Christine Peschken; Diane Kamen; Anca Askanase; Jill Buyon; Paul R Fortin

doi:10.1016/j.ard.2025.11.007

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, Murray Urowitz, John G Hanly, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Ann E Clarke, Sasha Bernatsky, Daniel Wallace, David IsenbergAnisur Rahman, Joan Merrill, Dafna D Gladman, Ian N Bruce, Michelle Petri, Ellen Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcόn, Ronald van Vollenhoven, Cynthia Aranow, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth Kalunian, Soren Jacobsen, Christine Peschken, Diane Kamen, Anca Askanase, Jill Buyon, Paul R Fortin

Afdeling for Rygkirurgi, Led- og Bindevævssygdomme HOC

Abstract

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Originalsprog	Engelsk
Tidsskrift	Annals of the Rheumatic Diseases
ISSN	0003-4967
DOI	https://doi.org/10.1016/j.ard.2025.11.007
Status	E-pub ahead of print - 12 dec. 2025

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10.1016/j.ard.2025.11.007

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Becker, Y. L. C., Boilard, É., Rollet-Labelle, E., Lood, C., Julien, A.-S., Abrahamowicz, M., Allaeys, I., Choi, M., Leclerc, J., Lévesque, T., Urowitz, M., Hanly, J. G., Gordon, C., Bae, S.-C., Romero-Diaz, J., Sanchez-Guerrero, J., Clarke, A. E., Bernatsky, S., Wallace, D., ... Fortin, P. R. (2025). Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality. Annals of the Rheumatic Diseases. Advance online publication. https://doi.org/10.1016/j.ard.2025.11.007

Becker, YLC, Boilard, É, Rollet-Labelle, E, Lood, C, Julien, A-S, Abrahamowicz, M, Allaeys, I, Choi, M, Leclerc, J, Lévesque, T, Urowitz, M, Hanly, JG, Gordon, C, Bae, S-C, Romero-Diaz, J, Sanchez-Guerrero, J, Clarke, AE, Bernatsky, S, Wallace, D, Isenberg, D, Rahman, A, Merrill, J, Gladman, DD, Bruce, IN, Petri, M, Ginzler, E, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Alarcόn, GS, van Vollenhoven, R, Aranow, C, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, K, Jacobsen, S, Peschken, C, Kamen, D, Askanase, A, Buyon, J & Fortin, PR 2025, 'Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality', Annals of the Rheumatic Diseases. https://doi.org/10.1016/j.ard.2025.11.007

@article{412bf531d7d1473a92b34c206747d644,

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

abstract = "OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.",

author = "Becker, {Yann L C} and {\'E}ric Boilard and Emmanuelle Rollet-Labelle and Christian Lood and Anne-Sophie Julien and Michal Abrahamowicz and Isabelle Allaeys and May Choi and Joannie Leclerc and Tania L{\'e}vesque and Murray Urowitz and Hanly, {John G} and Caroline Gordon and Sang-Cheol Bae and Juanita Romero-Diaz and Jorge Sanchez-Guerrero and Clarke, {Ann E} and Sasha Bernatsky and Daniel Wallace and David Isenberg and Anisur Rahman and Joan Merrill and Gladman, {Dafna D} and Bruce, {Ian N} and Michelle Petri and Ellen Ginzler and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and Alarcόn, {Graciela S} and {van Vollenhoven}, Ronald and Cynthia Aranow and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and Kenneth Kalunian and Soren Jacobsen and Christine Peschken and Diane Kamen and Anca Askanase and Jill Buyon and Fortin, {Paul R}",

year = "2025",

month = dec,

day = "12",

doi = "10.1016/j.ard.2025.11.007",

language = "English",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality

AU - Becker, Yann L C

AU - Boilard, Éric

AU - Rollet-Labelle, Emmanuelle

AU - Lood, Christian

AU - Julien, Anne-Sophie

AU - Abrahamowicz, Michal

AU - Allaeys, Isabelle

AU - Choi, May

AU - Leclerc, Joannie

AU - Lévesque, Tania

AU - Urowitz, Murray

AU - Hanly, John G

AU - Gordon, Caroline

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Clarke, Ann E

AU - Bernatsky, Sasha

AU - Wallace, Daniel

AU - Isenberg, David

AU - Rahman, Anisur

AU - Merrill, Joan

AU - Gladman, Dafna D

AU - Bruce, Ian N

AU - Petri, Michelle

AU - Ginzler, Ellen

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Alarcόn, Graciela S

AU - van Vollenhoven, Ronald

AU - Aranow, Cynthia

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, Kenneth

AU - Jacobsen, Soren

AU - Peschken, Christine

AU - Kamen, Diane

AU - Askanase, Anca

AU - Buyon, Jill

AU - Fortin, Paul R

PY - 2025/12/12

Y1 - 2025/12/12

N2 - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

AB - OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

U2 - 10.1016/j.ard.2025.11.007

DO - 10.1016/j.ard.2025.11.007

M3 - Journal article

C2 - 41390302

SN - 0003-4967

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

ER -

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

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