Abstract | OBJECTIVES: METHODS:
IgM anti-PC and anti-MDA in SLE patients (n=114) were compared with age- and sex-matched population-based controls (n=108). Common carotid intima-media thickness (IMT) and plaque occurrence were determined by B-mode ultrasound. Plaques were graded according to echogenicity (potentially vulnerability). Production of IgM anti-PC and anti-MDA by B cells was determined by ELISA and ELISPOT. The effect of anti-PC and anti-MDA on macrophage uptake of apoptotic cells and oxidative stress was studied by flow cytometry. RESULTS: Above 66rd percentile together, IgM anti-PC and anti-MDA were striking protection markers for plaque prevalence and echolucency in SLE (OR: 0.08, CI: 0.01-0.46 and OR: 0.10, CI: 0.01-0.82), respectively, and risk markers for plaque prevalence when below 33rd percentile: OR: 3.79, CI: (1.10-13.00). In vitro, IgM anti-PC and anti-MDA were much higher when B cells were co-cultured with CD3 T cells. Anti-HLA-, anti-CD40 antibody or CD40 silencing abolished these effects. Uptake of apoptotic cells was increased by IgM anti-PC and anti-MDA. MDA induced increased oxidative stress, which was inhibited by IgM anti-MDA. CONCLUSIONS: Unexpectedly, both IgM anti-MDA and IgM anti-PC are T-cell dependent and especially together, are strong protection markers for atherosclerosis in SLE. Underlying mechanisms include increased phagocytosis of apoptotic cells and decrease of oxidative stress.
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Authors | Mizanur Rahman, Sudhir Sing, Zahra Golabkesh, Roland Fiskesund, Thomas Gustafsson, Tomas Jogestrand, Anna G Frostegård, Ingiäld Hafström, Anquan Liu, Johan Frostegård |
Journal | Clinical immunology (Orlando, Fla.)
(Clin Immunol)
Vol. 166-167
Pg. 27-37
(05 2016)
ISSN: 1521-7035 [Electronic] United States |
PMID | 27102765
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- CD3 Complex
- Immunoglobulin M
- Phosphorylcholine
- Malondialdehyde
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Topics |
- Adult
- Apoptosis
(immunology)
- Atherosclerosis
(complications, immunology, metabolism)
- B-Lymphocytes
(immunology, metabolism)
- Biomarkers
(metabolism)
- CD3 Complex
(immunology, metabolism)
- Carotid Intima-Media Thickness
- Cells, Cultured
- Coculture Techniques
- Enzyme-Linked Immunosorbent Assay
- Enzyme-Linked Immunospot Assay
- Female
- Humans
- Immunoglobulin M
(immunology, metabolism)
- Jurkat Cells
- Lupus Erythematosus, Systemic
(complications, immunology, metabolism)
- Male
- Malondialdehyde
(immunology, metabolism)
- Middle Aged
- Oxidative Stress
(immunology)
- Phagocytosis
(immunology)
- Phosphorylcholine
(immunology, metabolism)
- Plaque, Atherosclerotic
(diagnostic imaging, immunology)
- T-Lymphocytes
(immunology, metabolism)
- Ultrasonography
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