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 leve ls of circulating IgA and is characterized by deposition of primarily IgA1 in the renal mesangium. It has not yet been clarified which mechanisms gove rn the deposition of IgA1 in the mesangium. One of the factors which may pl ay a role in trapping of IgA in the mesangial area is the interaction of Ig A with specific IgA receptors (Fc alpha R, CD89) on the mesangial cells. Methods. In the present study IgA. derived from patients with IgAN and cont rols 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 d ependent 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 comp ared to controls showed no significant difference. However these experiment s are affected by differences in IgA concentration and combinations of diff erent sizes of IgA. Using purified fractions of mIgA, dIgA, and pIgA isolat ed from serum, a significantly reduced binding of mIgA. to CD89 from patien ts 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 dire ct role for CD89 in deposition of IgA. However reduced binding of mIgA to C D89 may affect IgA clearance, leading to higher serum IgA. Furthermore, sin ce 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 .