Autoimmune and proinflammatory activity of oxidized immunoglobulins.
OBJECTIVE
Oxidation reactions can modify protein activity or specificity. Recently, a novel redox-reactive family of autoantibodies was described, which indicated involvement of altered antibodies (beside altered antigens) into autoimmune reactions. The aim of our study was to determine the binding capacity alterations of electro-oxidized blood donors' IgGs, and to evaluate their effects on released proinflammatory interleukin 6 in HUVEC.


RESULTS
We found out that 1.) Isolated blood donor IgGs bound after electro-oxidation to beta2-glycoprotein I, cardiolipin, citrullinated cyclic peptide and protein 3 by enzyme-linked immunosorbent assay, extractable nuclear antigens by counterimmuno-electrophoresis, and cell antigens by indirect immunofluorescence; 2.) Alterations in immunoreactivity of IgGs due to oxidation highly depend on electric current, time of exposure and the presence of antioxidants, 3.) Treatment of HUVEC with oxidized IgGs resulted in changed cell morphology, accompanied by an increase in released interleukin-6.


CONCLUSIONS
Our data suggest repeatable transformation of antibodies present in the blood of healthy persons and patients. Inter-individual differences in chemical stability of antibodies, patient's antioxidant status, and the microenvironmental changes at the cellular level may influence the range of antibody alterations and their involvement in pathophysiological autoimmune processes.
Omersel
J
J
University Medical Centre, Division of Internal Medicine, Department of Rheumatology, Vodnikova 62, SI-1000 Ljubljana, Slovenia.
Jurgec
I
I
Cucnik
S
S
Kveder
T
T
Rozman
B
B
Sodin-Semrl
S
S
Bozic
B
B
D000918:Antibody Specificity; D000975:Antioxidants / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001782:Blood Donors; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism
D000975:Antioxidants; D001323:Autoantibodies; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger