| Author/Editor | Artenjak, Andrej; Omersel, Jasna; Ahlin Grabnar, Pegi; Mlinarič-Raščan, Irena; Shoenfeld, Yehuda; Sodin-Šemrl, Snežna; Božič, Borut; Čučnik, Saša | |
| Title | Oxidatively altered IgG with increased immunoreactivity to [beta]2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells | |
| Type | članek | |
| Vol. and No. | Letnik 24, št. 4/5 | |
| Publication year | 2015 | |
| Volume | str. 448-462 | |
| ISSN | 0961-2033 - Lupus | |
| Language | eng | |
| Abstract | Oxidative stress has been shown to play a role in modifying antibodies in favor of higher auto- immunoreactivity. We studied the immunoreactivity of oxidized IgG (oxIgG) to beta2-glycopro- tein I ( beta2GPI), six peptide sequences corresponding to amino acid clusters on its different domains, to determine their effects on human coronary artery endothelial cells (HCAEC). Human IgG was purified from seven donors, electro-oxidized and checked for immunoreac- tivity and avidity to beta2GPI and to peptides by ELISA. Conformational stability and antibody- antigen complex formation of oxIgG was analyzed by fluorescence spectroscopy and dynamic light scattering. Resting and activated sub-confluent HCAEC were stimulated with oxIgG or IgG. Secreted cytokines were measured by ELISA. Immunoreactivity of seven oxIgG samples increased to 7.5-fold against beta2GPI and to 3.8-fold against six peptides as compared to IgG. oxIgG showed low avidity properties. Conformational changes and exposure of protein hydrophobic regions were confirmed by an elevation in fluorescence (2.4- to 5.0-fold) on bis- ANS dye binding to oxIgG. oxIgG significantly elevated the release of GROalpha and IL-8 in resting and activated states of HCAEC. Oxidation alters IgG in favor of autoreactivity toward whole beta2GPI and corresponding peptides on different domains of beta2GPI and could lead to dysfunction of arterial endothelium by upregulation of chemokines. | |
| Keywords | beta2-glycoprotein electro-oxidation coronary artery endothelial cells beta2-glikoproteina elektro-oksidacije endotelijske celice koronarnih arterij |