title: Enhanced recognition of reactive oxygen species damaged human serum albumin by circulating systemic lupus erythematosus autoantibodies.
abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore, we hypothesized that oxidative by-products, such as hydroxyl radical (*OH), could lead to neoantigens like *OH damaged human serum albumin (HSA), which could in turn initiate autoimmunity in SLE. In the present study, the binding characteristics of SLE autoantibodies with native and *OH damaged HSA were assessed. SLE patients (n = 74) were examined by direct binding ELISA and the results were compared with healthy age- and sex-matched controls (n = 44). High degree of specific binding by 52.7% of patients sera towards *OH damaged HSA, in comparison to its native analogue (p < 0.05) was observed. Normal human sera showed negligible binding with either antigen. Competitive ELISA and gel retardation assays reiterate the direct binding results. The increase in total serum protein carbonyl levels in the SLE patients was largely due to an increase in oxidized albumin. HSA of SLE patients (SLE-HSA) and normal subjects (normal-HSA) were purified. Spectroscopic analysis confirmed that the SLE-HSA samples contained higher levels of carbonyls than normal-HSA (p < 0.01). SLE-HSA was conformationally altered, with more exposure of its hydrophobic regions. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in SLE patients.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, AMU, Aligarh, India. zrasheed@rediffmail.com
authors.forename: Zafar
authors.initials: Z
authors.lastname: Rasheed
authors.forename: Zafar
authors.initials: Z
authors.lastname: Sheikh
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmad
authors.forename: Naila
authors.initials: N
authors.lastname: Rasheed
authors.forename: Naila
authors.initials: N
authors.lastname: Sheikh
authors.forename: Rashid
authors.initials: R
authors.lastname: Ali
authors.forename: Rashd
authors.initials: R
authors.lastname: Ali
mesh_terms: D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D017665:Hydroxyl Radical / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008875:Middle Aged; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D012709:Serum Albumin; D017665:Hydroxyl Radical