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Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0003-3161-0402
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2018 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, article id 36Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Immunoglobulin M (IgM) autoreactivity to malondialdehyde (MDA) protein modifications is part of the natural antibody repertoire in health and may have beneficial functions. In contrast, IgG anti-MDA are increased in chronic inflammation and autoimmunity and may instead have pathogenic properties.

METHODS: Herein, we investigated serum IgG anti-MDA levels by enzyme-linked immunosorbent assay (ELISA) in 398 systemic lupus erythematosus (SLE) patients in the Swedish Karolinska SLE cohort and compared these to findings in 225 US SLE patients from New York University and Johns Hopkins University.

RESULTS: In two independent cohorts, IgG anti-MDA levels correlated positively with disease activity by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; p < 0.0001, Spearman R = 0.3). Meta-analysis found an odds ratio of 2.7 (confidence interval (CI) 1.9-3.9; p < 0.0001) for high anti-MDA IgG levels with active disease (SLEDAI ≥ 6). Furthermore, IgG anti-MDA correlated directly with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), soluble tumor necrosis factor receptors (sTNFR-1, sTNFR-2), and vascular cell adhesion molecule 1 (VCAM-1) measurements, and inversely with complement factors (C1q, C2, C3, C4). Importantly, IgG anti-MDA levels were significantly elevated in SLE patients with active nephritis (p = 0.0005) and correlated with cystatin C estimated glomerular filtration rate and albuminuria.

CONCLUSIONS: Elevated IgG anti-MDA in SLE patients was associated with high disease activity, with active lupus nephritis, and with biomarkers of systemic inflammation. This natural antibody reactivity may have potential prognostic utility, and may also actively contribute to pathogenesis.

Place, publisher, year, edition, pages
2018. Vol. 20, article id 36
Keywords [en]
Autoantibodies, Disease activity, Lupus nephritis, MDA, Malondialdehyde protein modification, Natural antibodies, SLE
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-345090DOI: 10.1186/s13075-018-1530-2ISI: 000426328200004PubMedID: 29482604OAI: oai:DiVA.org:uu-345090DiVA, id: diva2:1188568
Funder
Swedish Research CouncilÅke Wiberg FoundationMagnus Bergvall FoundationSwedish Heart Lung FoundationSwedish Rheumatism AssociationKing Gustaf V Jubilee FundNIH (National Institute of Health), R01 AR043727NIH (National Institute of Health), R01 AR069572Stockholm County CouncilAvailable from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-04-26Bibliographically approved

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