Autoimmune reactivity of IgM acquired after oxidation

• Published in: Redox report : communications in free radical research 2011-11, Vol.16 (6), p.248-256
• Main Authors: Omersel, Jasna, Avberšek-Lužnik, Ivica, Grabnar, Pegi Ahlin, Kveder, Tanja, Rozman, Blaž, Božicˇ, Borut
• Format: Article
• Language: English
• Subjects: Adult; Antibody Specificity; Antigen-Antibody Reactions; Autoantigens - immunology; Autoantigens - metabolism; Autoimmune disease; beta 2-Glycoprotein I - immunology; Binding Sites, Antibody; Cardiolipins - immunology; Electrochemistry; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Hemin - pharmacology; Humans; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunoglobulin M - metabolism; Male; Natural autoantibodies; Oxidation; Oxidation-Reduction; Oxidative Stress; Phenylhydrazines - metabolism; Protein Carbonylation; Protein Processing, Post-Translational; Redox-reactive antibodies; Rheumatoid Factor - immunology
• ISSN: 1351-0002; 1743-2928
• DOI: 10.1179/174329211X13190184351680

Objectives Redox-reactive antibodies, mainly of the IgG class, gained a wide area of interest after their autoimmune reactivity was revealed following the application of chemical and physiological oxidants. In this study, we examined the susceptibility of IgMs to oxidation and evaluated their binding to the autoantigens important in some autoimmune diseases. Methods IgM and IgG fractions, isolated from healthy individuals' sera, were oxidized using direct electric current or physiological oxidant hemin. Specificities towards beta-2-glycoprotein I (β 2 -GPI), cardiolipin (CL), and rheumatoid factor were evaluated with the enzyme-linked immunosorbent assays (ELISAs). Post-translational modification was investigated by 2,4-dinitrophenylhydrazine reaction. Results Electrochemically oxidized IgM fractions exhibited altered immunoreactivity - low to medium titers in anti-CL and low positive titers in anti-β 2 -GPI ELISA but exhibited no rheumatoid factor reactivity. Oxidized IgG and IgM fractions exhibited 2.5- and 5-fold increase in the carbonyl content, respectively. Discussion An increase in the carbonyl content along with increased immunoreactivity after oxidation suggests modifications of the IgM paratopes. These results point towards possible modifications of native IgMs to their autoimmune state despite the fact that IgMs were less susceptible to oxidation than IgGs. The importance of an individual's redox status in maintenance of autoimmune reactions was emphasized by in vitro diagnostic tests.