Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by circulating and tissue fixed autoantibodies reactive with self-antigens, including nucleic acid and other nuclear components. The pathways by which these autoantibodies act as a pathogenic factor remain elusive. Present study has investigated the role of estrogens in SLE etiopathogenesis. Estrogen-modified DNA [4-OHE(2)-Cu(II)-DNA] showed single- and double-strand breaks, hyperchromicity, decrease in Tm, and modification of bases. The 4-OHE(2)-Cu(II)-DNA exhibited increased binding with naturally occurring anti-DNA autoantibodies as compared to the unmodified native form (P < 0.001) as assessed by ELISA, quantitative precipitin titration, and gel retardation assay. The relative affinity of anti-DNA antibodies for modified and native DNA was in the order of 2.1 x 10(-7) M and 1.3 x 10(-6) M, respectively. The data suggested that DNA modified with 4-OHE(2) and Cu(II) may be one of the factors for the induction of circulating anti-DNA autoantibodies in SLE.

Glutamic acid decarboxylase-65 (GAD(65)) is an immunological marker of type 1 autoimmune diabetes. High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). Binding specificity of isolated IgG of patients (n = 17) from each diabetic group and control group (n = 10) was checked by inhibition enzyme linked immunosorbent assay (ELISA) and quantitative precipitin titration assay. Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease.

No abstract

High binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.

The median-term postpartum prognosis of HIV-infected pregnant women with access to HAART is good. Exposure to short-course ZDVm or START during pregnancy did not jeopardize their response to subsequent therapy.

Aging causes gradual changes in free radicals, antioxidants, and immune-imbalance in the elderly. This study aims to understand links among aging, gluco-oxidative stress, and autoantibodies in asymptomatic individuals. In vitro glycation of human serum albumin (Gly-HSA) induces appreciable biochemical changes. Significant inhibition of advanced glycation end products (AGEs) formation was achieved using garlic extract (53.75%) and epigallocatechin-3-gallate from green tea (72.5%). Increased amounts of serum carbonyl content (2.42 ± 0.5) and pentosidine (0.0321 ± 0.0029) were detected in IV-S (S represent smokers) vs. IV group individuals. Direct binding ELISA results exhibited significantly high autoantibodies against Gly-HSA in group IV-S (0.55 ± 0.054; p < 0.001) and III-S (0.40 ± 0.044; p < 0.01) individuals as compared to the age matched subjects who were non-smokers (group IV and III). Moreover, high average percent inhibition (51.3 ± 4.1%) was obtained against Gly-HSA in IV-S group individuals. Apparent association constant was found to be high for serum immunoglobulin-G (IgG) from group IV-S (1.18 × 10−6 M) vs. serum IgG from IV group (3.32 × 10−7 M). Aging induced gluco-oxidative stress and AGEs formation may generate neo-epitopes on blood-proteins, contributing to production of autoantibodies in the elderly, especially smokers. Use of anti-glycation natural products may reduce age-related pathophysiological changes.

Background: Glycated proteins present new immunological epitopes on their surface against which autoantibodies are generated that have a possible role in immunopathogenesis in diabetic complications. Methods: In the present study, in vitro glycation- and reactive oxygen species (ROS)-modified human serum albumin (HSA) has been studied by different spectroscopic techniques (UV and fluorescence) and thermal denaturation profiles. The binding characteristics of circulating autoantibodies in diabetic patients and diabetic patients with secondary complications against native HSA (N-HSA) and ROS-modified glycated HSA (RG-HSA) were assessed by direct and competition enzyme-linked immunosorbent assay (ELISA). In another approach, antibodies against RG-HSA (RG-HSA-Abs) induced in experimental animals were used as an immunochemical probe for the detection of gluco-oxidative lesions in blood proteins of patients (n = 8) with diabetic retinopathy. Results: Modified RG-HSA showed marked structural changes. High recognition of RG-HSA was shown by diabetic serum autoantibodies. Diabetic patients with retinopathy, nephropathy and atherosclerosis showed significantly (p < 0.001) stronger binding to RG-HSA over N-HSA. Normal human sera exhibited negligible binding with either antigen. Competitive inhibition ELISA results show significantly high binding of RG-HSA-Abs to albumin, immunoglobulin G and red blood cell membrane isolated from diabetic retinopathic patients. Conclusion: In conclusion, these results suggest that hyperglycemia together with ROS may contribute to the immunopathogenesis of diabetes-associated complications.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which anti‐double‐stranded DNA antibody is a classic autoantibody that characterizes SLE. A role for oestrogens in the pathogenesis of SLE has been suspected for many years but the exact patho‐aetiology remains elusive. In this study, the binding of SLE autoantibodies with native and 4‐OHE2‐NO‐modified plasmid DNA were assessed. Binding specificity of antibodies was analysed by direct binding and inhibition enzyme‐linked immunosorbent assay, quantitative precipitin titration and gel retardation assay. Anti‐DNA IgG from SLE sera, purified on Protein A‐Agarose matrix, exhibited increased recognition of 4‐OHE2‐NO‐DNA than native DNA (P < 0.001). Gel retardation assay further substantiated the enhanced recognition of modified DNA by anti‐DNA autoantibodies. The affinity of anti‐DNA antibodies for modified polymer was found to be high as calculated by using Langmuir plot. DNA modified by 4‐OHE2‐NO presents unique neo‐epitopes that might be one of the factor in antigen‐driven induction of SLE autoantibodies.