Injection of recombinant FcalphaRI/CD89 in mice does not induce mesangial IgA deposition.
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.
van der Boog
Paul J M
PJ
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. p.j.m.van_der_boog@lumc.nl
van Kooten
Cees
C
van Zandbergen
Ger
G
Klar-Mohamad
Ngaisah
N
Oortwijn
Beatrijs
B
Bos
Nico A
NA
van Remoortere
Alexandra
A
Hokke
Cornelis H
CH
de Fijter
Johan W
JW
Daha
Mohamed R
MR
D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc; D011994:Recombinant Proteins
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D011994:Recombinant Proteins