Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy

Introduction. Patients with primary IgA nephropathy (IgAN) have an increased level of immunological memory to certain parenteral recall antigens. We recently found a deficient IgA1 immune response after intranasal challenge with a neo-antigen: cholera toxin subunit B. In the present study, we assessed the specific IgA1 and IgA2 antibody response in plasma, peripheral blood cells and mucosal secretions after primary enteral immunization. Methods. Twenty eight IgAN patients, 26 patients with non-immunological renal disease and 32 healthy subjects were immunized orally with three sequential doses of live, attenuated, Salmonella typhi Ty21a. The humoral immune response in body fluids and antibody synthesis by circulating B cells was assessed in specific ELISAs and ELIPSAs respectively. Results. Oral immunization resulted in significantly (P < 0.0001) increased IgM, IgG, IgA, IgA1 and IgA2 responses in all groups, both in plasma and in circulating B cells in vitro. The IgA1 response in plasma was significantly (P < 0.05) lower in IgAN patients, while no significant differences in IgM (P = 0.36), IgG (P = 0.79) or 1gA2 (P = 0.45) responses were found as compared with matched control groups. The amount of IgA1 synthesized by circulating B cells tended to be lower in IgAN patients. No significant IgA response after oral immunization with S. typhi Ty21a was found in saliva (P = 0.11) or tears (P = 0.10). Conclusions. These data suggest an IgA1 hyporesponsiveness in patients with IgAN that is not only apparent after primary challenge of the nasal-associated lymphoid tissue but also after presentation to the gut. Previous results after parenteral recall immunization may be explained by assuming that IgAN patients require more frequent and/or longer exposure to IgA1-inducing antigens on their mucosal surfaces before they reach protective mucosal immunity. As a consequence, overproduction of IgA1 antibodies occurs in the systemic compartment, accompanied by an increased number of IgA1 memory cells.