Induction of endothelial cell apoptosis by heat‐shock protein 60–reactive antibodies from anti–endothelial cell autoantibody–positive systemic lupus erythematosus patients
Abstract
Objective: To determine whether anti–endothelial cell autoantibodies (AECAs) from systemic lupus erythematosus (SLE) patients with the antiphospholipid syndrome are involved in the initial endothelial cell (EC) membrane perturbation effect that is postulated to provide a target for antiphospholipid antibody (aPL) binding and, hence, to trigger the thrombotic cascade. To identify the AECA antigenic target on ECs and to determine the mechanism whereby the EC membrane is disrupted. Methods: AECAs from SLE patients were assayed for binding to ECs by flow cytometry. Positive AECAs were assayed by immunoblotting, and a consensus antigen was identified by mass spectrometry. This candidate antigen was tested in recombinant form for AECA recognition. AECAs were affinity‐purified on this antigen and incubated with ECs to determine their physiologic effects. Anti‐Hsp60 antibody titers were determined by enzyme‐linked immunosorbent assay. The relationship of anti‐Hsp60 status and lupus anticoagulant (LAC) status to thrombotic manifestations between disease onset and the last followup visit were analyzed. Results: Most of the SLE sera (73%) possessed IgG that bound to the surface of ECs. These positive IgG shared reactivity against a 60‐kd EC surface polypeptide that was identified as human Hsp60. The presence of Hsp60 at the EC surface was established using anti‐Hsp60 antibodies from commercial sources or affinity‐purified from SLE sera that bound ECs. Incubation of ECs with these anti‐Hsp60 antibodies induced apoptosis in a time‐ and dose‐dependent manner, as determined by Hoechst 33342 dye staining of condensed nuclei and by annexin V binding to surface phosphatidylserine. Anti‐Hsp60 antibodies were not restricted to SLE patients, but were found in patients with other autoimmune diseases. However, anti‐Hsp60 antibodies were significantly associated with an increased frequency of thrombosis when present in combination with LAC in the SLE patients. Conclusion: The presence of Hsp60 at the surface of ECs serves as a target for the anti‐Hsp60 antibodies in SLE sera. These anti‐Hsp60 antibodies bind to ECs and induce apoptosis, particularly phosphatidylserine exposure, thus providing a target for the binding of aPL and inducing the subsequent thrombotic cascade.
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Antibodies targeting mitochondrial components other than mtDNA, including anti-cardiolipin, anti-HSP60, AMA-M3, and AMA-M5, are found in SLE.
“Antibodies targeting mitochondrial components other than mtDNA are also found in SLE. They include anti-cardiolipin [AMA-M1, also known as anti-cardiolipin antibodies (ACA)], anti-60kDa heat shock protein (anti-HSP60), as well as AMA-M3 and AMA-M5 antibodies.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [53]
Patients with SLE have antibodies against HSP60.
“Patients with SLE have antibodies against HSP6053, and their presence (when concomitant with anti-phospholid antibodies) is associated with vascular events54.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [53]
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Self-citationAbnormal Mitochondrial Physiology in the Pathogenesis of Systemic Lupus Erythematosus
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- Authors
- Dieudé, M., Senécal, J., & Raymond, Y.
- Affiliations
- Hôpital Notre-Dame (CA)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2004-10
- Volume
- 50
- Issue
- 10
- Pages
- 3221-3231
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2041001167
- Cited by
- 94
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 8 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP-36436)
- Centre Hospitalier de l'Université de Montréal
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- systemic lupus erythematosus, heat shock protein 60, endothelial cell apoptosis, antiphospholipid syndrome, lupus anticoagulant, thrombosis, endothelial cell membrane, autoantibody binding, autoimmune disease, phosphatidylserine, thrombotic microangiopathy
- MeSH terms
- Autoantibodies, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G, Lupus Erythematosus, Systemic, Male, Middle Aged, Thrombosis, Lupus Coagulation Inhibitor, Apoptosis, Chaperonin 60, Endothelial Cells
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