title: Significance of Lipid-Derived Reactive Aldehyde-Specific Immune Complexes in Systemic Lupus Erythematosus.
abstract: Even though systemic lupus erythematosus (SLE) is associated with high morbidity and mortality rates among young and middle-aged women, the molecular mechanisms of disease pathogenesis are not fully understood. Previous studies from our laboratory suggested an association between oxidative stress and SLE disease activity (SLEDAI). To further assess the role of reactive oxygen species (ROS) in SLE, we examined the contribution of lipid-derived reactive aldehydes (LDRAs)-specific immune complexes in SLE. Sera from 60 SLE patients with varying SLEDAI and 32 age- and gender- matched healthy controls were analyzed for oxidative stress and related markers. Patients were divided into two groups based on their SLEDAI scores (<6 and ≥ 6). Both SLEDAI groups showed higher serum 4-hydroxynonenal (HNE)-/malondialdehyde (MDA)-protein adducts and their specific immune complexes (HNE-/MDA-specific ICs) together with IL-17 than the controls, but the levels were significantly greater in the high SLEDAI (≥ 6) group. Moreover, the serum levels of anti-oxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase (CAT) were significantly reduced in both patient groups compared to controls. Remarkably, for the first time, our data show that increased HNE-/MDA-specific ICs are positively associated with SLEDAI and elevated circulating immune complexes (CICs), suggesting a possible causal relationship among oxidative stress, LDRA-specific ICs and the development of SLE. Our findings, apart from providing firm support to an association between oxidative stress and SLE, also suggest that these oxidative stress markers, especially the HNE-/MDA-specific ICs, may be useful in evaluating the prognosis of SLE as well as in elucidating the mechanisms of disease pathogenesis.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Gangduo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Pierangeli
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Rohan
authors.initials: R
authors.lastname: Willis
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Emilio B
authors.initials: EB
authors.lastname: Gonzalez
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: M Firoze
authors.initials: MF
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000097:blood / Q000737:chemistry*; D000936:Antigen-Antibody Complex / Q000097:blood*; D001798:Blood Proteins / Q000737:chemistry; D016022:Case-Control Studies; D002374:Catalase / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000737:chemistry; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000447:Aldehydes; D000936:Antigen-Antibody Complex; D001798:Blood Proteins; D020381:Interleukin-17; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal