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Clinical and Vaccine Immunology, March 2008, p. 412-417, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00373-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Local Immune Response to Upper Urinary Tract Infections in Children

Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland,¹ Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland,² National Public Health Institute, Turku, Finland,³ Department of Pediatrics, Turku University Central Hospital, Turku, Finland,⁴ Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland⁵

Received 10 September 2007/ Returned for modification 19 November 2007/ Accepted 17 December 2007

Vaccines are needed against urinary tract infections (UTIs) in children, as episodes of pyelonephritis (PN) may cause renal scarring. Local immune mechanisms are regarded to confer protection, yet they have been poorly characterized for children. This study explores the local immune response in children by looking for newly activated pathogen-specific antibody-secreting cells (ASC), expected to appear transiently in the circulation as a response to UTI. Urinary tract-originating ASC specific to each patient's own pathogen or P fimbria were studied in 37 children with PN. The children were examined for recidivism and renal scarring in a 6-month follow-up study. Pathogen-specific ASC were found in 33/37 children, with the magnitude increasing with age. In contrast to the case for adults, with immunoglobulin A (IgA) dominance, in 18/33 cases IgM dominated the response, and this occurred more frequently in infants (63%) than in older children (30%). The most vigorous response was found to whole Escherichia coli bacteria (geometric mean, 63 ± 2,135 ASC/10⁶ peripheral blood mononuclear cells [PBMC]), yet responses were found to P fimbriae (13 ± 33 ASC/10⁶ PBMC), too. The response peaked at 1 to 2 weeks and was low/negligible 3 to 7 weeks after the beginning of symptoms. Recidivism was seen in seven patients, and renal scarring was seen in nine patients. In conclusion, a response of circulating ASC was found in children with UTIs, with the magnitude increasing with age. Since IgM is not present in urine, the IgM dominance of the response suggests that systemic immune mechanisms are more important in the immune defense in children than in adults. In 81% of patients, no recidivism was seen, suggesting a successful immune defense.

Published ahead of print on 9 January 2008.