Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis

Arthritis Research & Therapy

Anders Larsson¹  Jill P. Buyon²  Robert M. Clancy²  Gregg J. Silverman²  Iva Gunnarsson³  Uta Hardt³  Elisabet Svenungsson³  Caroline Grönwall³  Michelle Petri⁴ 

[1] Department of Medical Sciences, Clinical Chemistry, Uppsala University;Department of Medicine, Division of Rheumatology, NYU School of Medicine;Department of Medicine, Rheumatology Unit, Karolinska Institutet and Karolinska University Hospital, Center for Molecular Medicine;Department of Rheumatology, Johns Hopkins University School of Medicine;

关键词: Autoantibodies;    Natural antibodies;    Malondialdehyde protein modification;    SLE;    Lupus nephritis;    Disease activity;   

DOI  :  10.1186/s13075-018-1530-2

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown