Reduced binding of immunoglobulin A (IgA) from patients with primary IgA nephropathy to the myeloid IgA Fc-receptor, CD89 |
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Authors: | van Zandbergen G; van Kooten C; Mohamad N; Reterink T; de Fijter J; van de Winkel J; Daha M |
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Institution: | Department of Nephrology, Leiden University Medical Center, Building 1, C3P, PO Box 9600, 2300 RC, Leiden, The Netherlands; Department of Immunology, University Hospital, Utrecht, The Netherlands; Medarex Europe, Utrecht, The Netherlands; Corresponding author |
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Abstract: | Background. Primary IgA nephropathy (IgAN) is
associated with elevated levels of circulating IgA and is characterized by
deposition of primarily IgA1 in the renal mesangium. It has not yet been
clarified which mechanisms govern the deposition of IgA1 in the mesangium.
One of the factors which may play a role in trapping of IgA in the
mesangial area is the interaction of IgA with specific IgA receptors
(Fc&agr;R, CD89) on the mesangial cells. Methods.
In the present study IgA derived from patients with IgAN and
controls was investigated for its interaction with human CD89, expressed on
the surface of the murine B cell line IIA1.6. Results.
IgA binding to Cd89 expressing cells was specific, concentration
dependent and binding of dIgA and pIgA occurred in a more efficient fashion
than that of mIgA. IgA binding to CD89 directly from serum of patients
compared to controls showed no significant difference. However these
experiments are affected by differences in IgA concentration and
combinations of different sizes of IgA. Using purified fractions of mIgA,
dIgA, and pIgA isolated from serum, a significantly reduced binding of mIgA
to CD89 from patients compared to controls was observed. Finally, the
binding of aIgA2 to CD89 was less inhibited using mIgA from patients with
IgAN compared to controls. Conclusions. The reduced
binding of mIgA to CD89 seems to contradict a direct role for CD89 in
deposition of IgA. However reduced binding of mIgA to CD89 may affect IgA
clearance, leading to higher serum IgA. Furthermore, since it has been
demonstrated that mIgA can interfere with binding of di- and pIgA
deposition in the mesangial area. |
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