BACKGROUND: Earlier studies have suggested that complexes of the human IgA receptor FcalphaRI/CD89 with mouse IgA are pathogenic upon deposition in the renal mesangium. Transgenic mice expressing FcalphaRI/CD89 on macrophages/monocytes developed massive mesangial IgA deposition and a clinical picture of IgA nephropathy (IgAN). Based on these findings, the purpose of this study was to design an experimental model of IgAN by injection of human CD89 in mice. The interaction of mouse IgA with CD89 was investigated further. METHODS: Recombinant human soluble CD89 and a chimeric CD89-Fc protein were generated, produced, purified and injected in mice. Renal cryosections were stained for IgA and CD89. The interaction of mouse IgA with CD89 was analysed by fluorescence-activated cell sorting (FACS) analysis, enzyme-linked immunosorbent assay (ELISA) and plasmon resonance technology. RESULTS: Injection of recombinant human CD89 did not result in significant IgA or CD89 deposition in the renal mesangium. However, CD89 staining in the liver was found to be positive. CD89 was rapidly cleared from circulation without signs of complex formation with IgA. FACS analysis, ELISA and plasmon resonance techniques all revealed a dose-dependent binding of human IgA to recombinant CD89, while no detectable binding was seen of mouse IgA, either of serum IgA or of different monoclonal mouse IgA preparations. CONCLUSIONS: An experimental model for IgAN in mice could not be obtained by injection of recombinant CD89. This is compatible with our in vitro biochemical data showing a lack of binding between recombinant human CD89 and mouse IgA.
BACKGROUND: Earlier studies have suggested that complexes of the humanIgA receptor FcalphaRI/CD89 with mouseIgA are pathogenic upon deposition in the renal mesangium. Transgenic mice expressing FcalphaRI/CD89 on macrophages/monocytes developed massive mesangial IgA deposition and a clinical picture of IgAnephropathy (IgAN). Based on these findings, the purpose of this study was to design an experimental model of IgAN by injection of humanCD89 in mice. The interaction of mouseIgA with CD89 was investigated further. METHODS: Recombinant human soluble CD89 and a chimeric CD89-Fc protein were generated, produced, purified and injected in mice. Renal cryosections were stained for IgA and CD89. The interaction of mouseIgA with CD89 was analysed by fluorescence-activated cell sorting (FACS) analysis, enzyme-linked immunosorbent assay (ELISA) and plasmon resonance technology. RESULTS: Injection of recombinant humanCD89 did not result in significant IgA or CD89 deposition in the renal mesangium. However, CD89 staining in the liver was found to be positive. CD89 was rapidly cleared from circulation without signs of complex formation with IgA. FACS analysis, ELISA and plasmon resonance techniques all revealed a dose-dependent binding of humanIgA to recombinant CD89, while no detectable binding was seen of mouseIgA, either of serum IgA or of different monoclonal mouseIgA preparations. CONCLUSIONS: An experimental model for IgAN in mice could not be obtained by injection of recombinant CD89. This is compatible with our in vitro biochemical data showing a lack of binding between recombinant humanCD89 and mouseIgA.
Authors: Michelle M Gomes; Stephanie B Wall; Kazuo Takahashi; Jan Novak; Matthew B Renfrow; Andrew B Herr Journal: Biochemistry Date: 2008-10-01 Impact factor: 3.162
Authors: Sucharitha Balu; Rajko Reljic; Melanie J Lewis; Richard J Pleass; Richard McIntosh; Cees van Kooten; Marjolein van Egmond; Stephen Challacombe; Jenny M Woof; Juraj Ivanyi Journal: J Immunol Date: 2011-01-21 Impact factor: 5.422
Authors: Laureline Berthelot; Christina Papista; Thiago T Maciel; Martine Biarnes-Pelicot; Emilie Tissandie; Pamela H M Wang; Houda Tamouza; Agnès Jamin; Julie Bex-Coudrat; Aurelie Gestin; Ahmed Boumediene; Michelle Arcos-Fajardo; Patrick England; Evangéline Pillebout; Francine Walker; Eric Daugas; François Vrtosvnik; Martin Flamant; Marc Benhamou; Michel Cogné; Ivan C Moura; Renato C Monteiro Journal: J Exp Med Date: 2012-03-26 Impact factor: 14.307