Anti-native DNA antibodies from autoimmune sera also bind to DNA in mitochondria
Abstract
Sera from 20 patients with systemic lupus erythematosus (SLE), selected for elevated titers of antibody to native DNA (nDNA), were examined by indirect immunofluorescence (IF) on tissue culture Hep-2 and rabbit kidney cells. Twelve sera showed a particulate cytoplasmic staining, in addition to nuclear IF. Double IF staining by using a mouse monoclonal anti-nDNA and a human serum containing anti-mitochondrial antibody as probes showed that the cytoplasmic structures recognized by these 12 SLE sera were mitochondria. SLE sera showing mitochondrial staining had high anti-nDNA levels, as assessed by ELISA (3.5 +/- 1.9 O.D.), compared with those not showing this staining pattern (0.8 +/- 0.4 O.D.). Mitochondrial staining was abolished by DNase I pretreatment of the substrates. Liquid phase absorption of serum anti-nDNA with S1 nuclease-treated calf thymus DNA or purified mitochondrial DNA also removed staining. These findings demonstrate that anti-nDNA antibodies from patients with SLE bind to DNA in intact mitochondria. Therefore, mitochondrial IF staining on tissue culture cells in the presence of nuclear staining should be interpreted with caution, because the phenomenon could be entirely related to anti-native DNA. These observations might also provide new insights concerning the nature of immunogenic cellular components stimulating anti-DNA production.
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The anti-mitochondrial autoantibody repertoire and their antigenic targets remain mostly uncharacterized.
“Despite the extensive literature regarding antibodies targeting the cardiolipin (also known as the mitochondrial antigen M1) in SLE, the anti-mitochondrial autoantibody repertoire and their antigenic targets remains mostly uncharacterized (12, 34–37).”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [35]
Anti-mtDNA antibodies are induced in a subset of SLE patients.
“Studies showed that anti-mtDNA antibodies (AmtDNA) are induced in a subset of SLE patients, suggesting that extruded mtDNA could be a relevant source of antigen for the anti-double stranded DNA (anti-dsDNA) antibodies that prevail in SLE16,41,42.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [42]
Extruded mtDNA could be a relevant source of antigen for anti-dsDNA antibodies in SLE.
“Studies showed that anti-mtDNA antibodies (AmtDNA) are induced in a subset of SLE patients, suggesting that extruded mtDNA could be a relevant source of antigen for the anti-double stranded DNA (anti-dsDNA) antibodies that prevail in SLE16,41,42.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [42]
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Self-citation
- Authors
- Reimer, G., Rubin, R. L., Kotzin, B. L., & Tan, E. M.
- Affiliations
- Scripps Clinic (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1984-11-01
- Volume
- 133
- Issue
- 5
- Pages
- 2532-2536
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1949185997
- Cited by
- 22
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2013: 1
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- 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, mitochondrial DNA, mitochondrial staining, autoantibodies, cytoplasmic staining, antimitochondrial antibodies
- MeSH terms
- Animals, Antibodies, Antinuclear, Autoantigens, Autoimmune Diseases, Binding Sites, Antibody, Cell Line, DNA, DNA, Mitochondrial, Fluorescent Antibody Technique, Humans, Kidney, Lupus Erythematosus, Systemic, Mice, Inbred Strains, Mitochondria, Liver, Rabbits, Mice, Rats
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