Oxidation of α1-proteinase inhibitor by the myeloperoxidase hydrogen peroxidase system promotes binding to immunoglobulin A

We have demonstrated previously that patients with rheumatoid arthritis (RA) show an increase in serum and synovial fluid levels of complexes between alpha 1-proteinase inhibitor (alpha(1)PI) and IgA. These are believed to form through disulfide binding between the Cys(232) residue on alpha(1)PI and the penultimate cysteine residue (Cys(471)) Of the IgA alpha chain. The mechanism for this has not been elucidated. Ne show here that alpha(1)PI oxidized by the myeloperoxidase-hydrogen peroxide (MPO-H2O2) system promotes the formation of IgA-alpha(1)PI complexes when incubated with IgA and that such complexes have no inhibitory activity against porcine pancreatic elastase (PPE). The activity of alpha(1)PI was considerably reduced also in IgA-alpha(1)PI complexes isolated from serum of an RA patient, me suggest that formation of IgA-alpha(1)PI complexes in inflammation may involve oxidation of alpha(1)PI, and as a consequence the alpha(1)PI in such complexes has reduced elastase inhibitory activity. (C) 1999 Academic Press.