The binding of SLE autoantibodies to mitochondria
Open accessAbstract
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes. Because these complexes contain mitochondrial components, we assessed the presence of antibodies to whole mitochondria (wMITO) using an ELISA in which mitochondria from mouse liver are bound to microtiter plates pre-coated with poly-l-lysine. Studies with this ELISA demonstrated that SLE plasmas contain abundant anti-wMITO activity. While digestion with DNase 1 did not affect anti-wMITO activity, adsorption of plasma on DNA affinity columns could reduce binding activity. Assay for anti-mitochondrial antibodies (AMA) by immunofluorescence and an ELISA with the M2 antigen (2-oxo-acid dehydrogenase protein complex) showed a low frequency of positivity, indicating that AMA and anti-wMITO are distinct specificities. In the study of 204 patients with SLE, the levels of anti-wMITO were higher in active SLE and correlated with levels of anti-DNA. These findings suggest that anti-wMITO can form immune complexes with mitochondria which may drive pathogenesis.
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Immunoreactivity to intact mitochondria is increased in SLE sera compared with healthy individuals and is associated with increased disease activity.
“Immunoreactivity to intact mitochondria (owing to the presence of anti-whole mitochondria antibodies) is increased in the sera of patients with SLE compared with that of healthy individuals and is associated with increased disease activity230,261,262.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [262]
The Results (‘Relationship of anti-wMITO and disease activity’; page unavailable) report that antibodies to whole mitochondria are associated with higher SLE disease-activity scores. The Discussion says SLE sera bound well to intact mitochondria, and the Methods list healthy controls, but the retrieved passages do not establish that binding was higher in SLE sera than in healthy sera. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAntibodies to mitochondrial nucleic acids (mtDNA and mtRNA) are present in SLE or APS patients.
“Antibodies to mitochondrial nucleic acids (mtDNA and mtRNA) are also present in patients with SLE or APS230,231,261,262.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [262]
The Discussion (page unavailable) reports anti-DNA and anti-whole-mitochondrion reactivity in SLE patients, but says the DNA target could be mitochondrial, nuclear, or a cross-reactive antigen. The paper does not establish antibodies specifically to mtDNA or mtRNA, and it does not report findings in APS patients. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrevious studies reported possible associations between increased AMA levels and SLE clinical manifestations such as AVE and nephritis.
“Previous studies reported possible associations between increased AMA levels and SLE clinical manifestations [4,6 -9,12] such as AVE and nephritis.”
From Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality (2026) · cites this paper as [12]
The Results section, ‘Relationship of anti-wMITO and disease activity’ (page unavailable), associates anti-wMITO with urinary findings, and the Discussion describes an association with renal disease. But the paper distinguishes anti-wMITO from AMA and reports infrequent AMA positivity in SLE; it does not report an AMA association with nephritis or AVE. (LLM, conf=0.86)
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- Authors
- Pisetsky, D. S., Spencer, D. M., Mobarrez, F., Fuzzi, E., Gunnarsson, I., & Svenungsson, E.
- Affiliations
- Duke University (US)
- Uppsala University (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Pisetsky, David S.
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 212
- Pages
- 108349
- ISSN
- 1521-6616 (ISSN-L)
- PMC
- PMC10538439
- OpenAlex
- W3003059684
- Cited by
- 27
- References
- 61
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 3
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- systemic lupus erythematosus, autoantibodies, antimitochondrial antibodies, immune complexes, anti-DNA antibodies, disease activity, mouse liver mitochondria
- MeSH terms
- Animals, Antigen-Antibody Complex, Antibodies, Antinuclear, Autoantibodies, Autoantigens, Deoxyribonuclease I, DNA, Enzyme-Linked Immunosorbent Assay, Humans, Liver Cirrhosis, Biliary, Lupus Erythematosus, Systemic, Mitochondria, Mitochondria, Liver, Polylysine, Mass Spectrometry, Case-Control Studies, Mitochondrial Proteins, Proteomics, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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