Identification and characterization of IgA antibodies against β2-glycoprotein i in childhood Henoch-Schönlein purpura
Journal
British Journal of Dermatology
Journal Volume
167
Journal Issue
4
Pages
874-881
Date Issued
2012-10
Author(s)
Abstract
Background Henoch-Sch?nlein purpura (HSP) is a common IgA-mediated vasculitis in children. The antigenic target for IgA is to be determined. Objective To test whether β2-glycoprotein I (β2GPI) is an antigenic target for IgA in childhood HSP, and to evaluate the clinical implications and pathogenic role of such IgA autoantibodies. Methods The reactivity of patients' plasma samples and purified polyclonal IgA with β2GPI, β2GPI-derived peptides and endothelial cells was tested by enzyme-linked immunosorbent assay. The association between clinical manifestations and IgA anti-β2GPI antibodies was also analysed. Finally, IgA-mediated cytotoxicity on endothelial cells was further evaluated. Results At the acute stage, patients with HSP had significantly higher plasma levels of IgA antibodies against β2GPI than healthy controls [reference units (RU) 1·14 ± 0·8 vs. 0·42 ± 0·24, P < 0·001]. IgA anti-β2GPI antibodies were associated with the presence of joint manifestations (with vs. without joint involvement, 1·15 ± 0·64 vs. 0·85 ± 0·47, P = 0·0341) and heavy proteinuria (with vs. without heavy proteinuria, 2·09 ± 2·02 vs. 1·04 ± 0·62, P = 0·0028). Polyclonal IgA from plasma samples positive for IgA anti-β2GPI antibodies bound well not only to β2GPI with Kd values < 10-5 mol L-1, but also to some β2GPI-dereived linear peptides (P3, P5, P7, P11 and P12). Moreover, β2GPI-reactive polyclonal IgA also bound well to endothelial cells and induced complement-dependent cell lysis. Conclusion These findings reveal the clinical and pathogenic relevance of IgA anti-β2GPI antibodies in childhood HSP and suggest that β2GPI may be an important autoantigen for HSP. ? 2012 British Association of Dermatologists.
SDGs
Other Subjects
autoantibody; autoantigen; beta2 glycoprotein 1; immunoglobulin A antibody; adolescent; anaphylactoid purpura; arthralgia; article; blood sampling; child; childhood disease; clinical feature; controlled study; cytotoxicity; disease association; endothelium cell; enzyme linked immunosorbent assay; female; gastrointestinal hemorrhage; hematuria; human; human cell; immunoglobulin blood level; juvenile rheumatoid arthritis; male; nephrotic syndrome; pathogenesis; peptide synthesis; preschool child; priority journal; protein blood level; protein purification; proteinuria; school child; umbilical vein endothelial cell; Adolescent; beta 2-Glycoprotein I; Case-Control Studies; Child; Child, Preschool; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin A; Male; Purpura, Schoenlein-Henoch
Publisher
Oxford : Blackwell Scientific Publications
Type
journal article