Reduced binding of immunoglobulin A (IgA) from patients with primary IgA nephropathy to the myeloid IgA Fc-receptor, CD89.
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 alphaR, 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, CD89 could still contribute to pIgA deposition in the mesangial area.
van Zandbergen
G
G
Department of Nephrology, Leiden University Medical Center, The Netherlands.
van Kooten
C
C
Mohamad
N K
NK
Reterink
T J
TJ
de Fijter
J W
JW
van de Winkel
J G
JG
Daha
M R
MR
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D005591:Chemical Fractionation; D005260:Female; D005434:Flow Cytometry; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D014162:Transfection
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc