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  • Title: Identification and characterization of IgA antibodies against β2-glycoprotein I in childhood Henoch-Schönlein purpura.
    Author: Yang YH, Chang CJ, Chuang YH, Hsu HY, Yu HH, Lee JH, Wang LC, Lin YT, Chiang BL.
    Journal: Br J Dermatol; 2012 Oct; 167(4):874-81. PubMed ID: 22632612.
    Abstract:
    BACKGROUND: Henoch-Schönlein 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.
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