Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy

Abstract

Twelve IgA nephropathy (IgAN) patients and 18 controls were immunized with novel protein antigens, cholera toxin subunit B (CTB) via the nasal route and keyhole limpet hemocyanin (KLH) subcutaneously. Antibody secreting cells and antibody response in body fluids were determined by ELISPOT assay and ELISA, respectively. Analysis of variance showed, in contrast to controls (P < 0.001), no CTB-specific IgA response in the nasal washes of patients with IgAN. Significantly lower numbers of CTB-specific antibody-secreting cells in peripheral blood (P < 0.001) and CTB-specific antibodies in plasma (P < 0.005) were found in IgAN, both restricted to the IgA1 subclass. The proportions of CTB-specific IgA1-secreting cells in bone marrow aspirates correlated significantly with the corresponding ratios in plasma, with significantly lower values (P < 0.005) in IgAN as compared to controls. These results support the existence of a "mucosa-bone marrow axis" in humans, but no dysregulation of this axis was found in IgAN. The deficient mucosal IgA immune response to CTB observed in this study after primary mucosal immunization indicates that patients with IgAN have a defective immune response when challenged intranasally. These patients may depend on more frequent and/or prolonged antigen encounter at mucosal sites before efficient mucosal immunity is established. Repeated seeding of antigen-specific cells to secondary lympoid organs could result secondarily in the relative hyperresponsiveness found in IgAN upon reactivation by parenteral immunization.