Nephrology Dialysis Transplantation, Vol 14, Issue 2 353-359, Copyright © 1999 by Oxford University Press
J Roodnat, J de Fijter, C van Kooten, M Daha and L van Es
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 IgA2 (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
hyporesonsiveness 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. Key
words: IgA nephropathy; IgA subclasses; oral immunization;
S.typhi Ty21a
ORIGINAL ARTICLES
Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy
Department of Nephrology, C3-)23, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; Corresponding author
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