Autoimmune Reactions after Electro‐oxidation of IgG from Healthy Persons

Abstract

Proteins, including immunoglobulins, can be modified by oxidation. Extensive oxidation of immunoglobulins leads to denaturation and loss of biological activity, while initial steps of oxidation may change their specificity due to chemical alteration of the paratope. Electro-oxidation of the IgG fraction from healthy persons progress to auto-immunoreactivity, as shown for several autoantibodies including anti-beta2-glycoprotein I. Changes in immunoreactivity of IgG due to oxidative reactions highly depend on electric current and levels of serum antioxidants. Autoimmune reactions, leading to certain autoimmune diseases, may be partially a consequence of unbalanced antioxidative status of an individual.

Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

“…10 The validity of the oxidation reactions is strengthened by the fact that presence of vitamin C as an antioxidant protected IgG against alterations due to electro-oxidation. 10,36 Our group also showed that not only IgG but also IgM is prone to redoxreactions as shown by the increased binding to b2GPI and cardiolipin after oxidation. 7 Protein modifications, like increased carbonyl content, in oxidized fractions of IgG and IgM, 7 occurred because of direct electron-transfer or indirect oxidation with HOCl/ROS.…”

Electrohypersensitivity as a Newly Identified and Characterized Neurologic Pathological Disorder: How to Diagnose, Treat, and Prevent It

“…Moreover, as indicated in Table 5, we were able to show that, in peripheral blood, there is an increase in S100B protein in 15-20% of the patients and an increase in nitrosative stress-related nitrotyrosine (NTT) in 8-30% in the EHS and/or MCS groups, suggesting that these biomarkers may reflect opening of the blood-brain barrier (BBB) in these patients, whatever the patient group considered, since it was shown that S100B protein [15,16] and nitrotyrosine [17][18][19][20] are markers associated with BBB opening. In addition, we detected the presence of autoantibodies against O-myelin in about 20% of all cases, whether EHS, MCS or both; meaning that an autoimmune response against the white matter of the nervous system occurres in patients; a finding that may in fact be the consequence of the occurrence of oxidative/nitrosative stress [10,21]. Moreover, more recently, we measured different oxidative and nitrosative stress-related biomarkers such as thiobarbituric acid reactive substances (TBARS), oxidized glutathione (GSSG), and NTT in the peripheral blood of EHS patients.…”

Autoimmune reactivity of IgM acquired after oxidation

“…Serum was separated from freshly harvested blood of seven healthy donors (two men and five women, aged [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Donors were all non-smokers and had no presence of anti-cardiolipin antibodies (aCL), anti-β 2 -glycoprotein I antibodies (anti-β 2 -GPI), or rheumatoid factor (RF) antibodies determined by specific enzyme-linked immunosorbent assays (ELISAs).…”

“…A moderate increase in RF activity has been previously observed after the exposure of therapeutic polyclonal intravenous immunoglobulin to hematin but resulted in no further antigen-binding activity after treatment with ferrous (Fe 2+ ) ions. 39 Based on our previous experience, there are sera which lack redox-reactive antibodies under previously used conditions indicating intra and interindividual variability: Not all IgGs in polyclonal fraction are equally sensitive to oxidation 40 and IgM's susceptibility to oxidation, resulting in autoimmune activity, is even more restricted. Heme and hemin are known to induce toxicity through the generation of ROS and proinflammatory effects.…”