Exaggerated systemic antibody response to mucosal Helicobacter pylori infection in IgA nephropathy

Numerous studies in the literature report aberrant immune responsiveness in immunoglobulin A (IgA) nephropathy. However, all these studies investigate immune responses invoked by an artificially engineered antigen challenge. For the first time in IgA nephropathy, we report the systemic humoral respo nses generated as part of an active mucosal immune response against a commo n environmental pathogen, Helicobacter pylori(Hp). We studied 22 patients w ith IgA nephropathy and 9 controls without renal disease who were shown to be infected with Hp, using a C-13-urea breath test. Hp antigen-specific enz yme-linked immunosorbent assays were established to measure the anti-Hp IgA , IgG, and IgA and IgG subclass antibody levels. In addition, anti-Hp respo nses in the monomeric and polymeric (pIgA) fractions of serum IgA were meas ured after separation by gel filtration high-performance liquid chromatogra phy. IgA nephropathy was associated with both a greater rate of IgA anti-Hp seropositivity (P < 0.05) and a more pronounced IgA anti-Hp antibody respo nse (P < 0.01). In almost all cases, IgA anti-Hp was IgA1, and more than 90 % was polymeric. There was no difference in the frequency of IgG anti-Hp se ropositivity, but patients produced a much greater IgG anti-Hp response (P < 0.01). In addition, the IgG subclass responses were markedly different, w ith IgG1 predominant in controls and IgG2 and IgG3 the major subclasses pro duced in IgA nephropathy. We have shown an exaggerated systemic antibody re sponse to mucosal infection caused by Hp in patients with IgA nephropathy, predominantly consisting of pIgA1, IgG2, and IgG3. This suggests that in Ig A nephropathy, not only is pIgA1 production poorly controlled, but regulati on of IgG isotype switching in response to mucosal pathogens is also derang ed. (C) 1999 by the National Kidney Foundation, Inc.