Antibody-Secreting Cells in Acute Urinary Tract Infection as Indicators of Local Immune Response

Papunen, R; Virtanen, Elina; Möttönen, Timo; Räsänen, L; Ala-Kaila, K; Mäkelä, P H; Arvilommi, Heikki

doi:10.1093/infdis/169.5.1023

Cited by 29 publications

(46 citation statements)

References 57 publications

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“…We showed earlier that ASC specific to the pathogen can be found in the blood of adult patients for both lower and upper UTIs (18), and the present study was undertaken to look for a response in children. Since the mucosal immune response is believed to contribute to protection, it was of interest to look for signs of renal scarring during follow-up.…”

Section: Discussionmentioning

confidence: 95%

“…Specific ASC were enumerated by ELISPOT assay (5,12,17,18,27). In this assay, isolated lymphocytes are allowed to secrete antibodies into microtiter plate wells previously coated with the antigen of interest.…”

Section: Methodsmentioning

confidence: 99%

“…The next steps were described in detail earlier (12,17,18). Briefly, the nonspecific binding sites were blocked with 1% bovine serum albumin-PBS (30 min, 37°C), and then 10 5 cells in culture medium were incubated in each well (2 to 3 h, 37°C).…”

Section: Methodsmentioning

confidence: 99%

“…The local immune response to UTI has been investigated in adults by examining urinary tract-originating, newly recruited, pathogen-specific B cells in the peripheral blood. These cells are expected to be on their way back to the urinary mucosa to secrete antibodies locally (17,18). These cells have proven to have unique homing potentials, as interpreted by their expression of homing receptors (Kantele et al, unpublished results).…”

mentioning

confidence: 99%

“…Specific antibody responses to the infecting pathogen have been observed both in sera and in urines from both adults and children with UTIs (6,17,18,20,22,25,26,28), with the levels being considerably lower in children than in adults. The local immune response to UTI has been investigated in adults by examining urinary tract-originating, newly recruited, pathogen-specific B cells in the peripheral blood.…”

mentioning

confidence: 99%

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Local Immune Response to Upper Urinary Tract Infections in Children

Palkola

Arvilommi²,

Honkinen

et al. 2008

Clin Vaccine Immunol

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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/10 6 peripheral blood mononuclear cells [PBMC]), yet responses were found to P fimbriae (13 ؎ 33 ASC/10 6 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.Urinary tract infection (UTI) represents one of the most common infections encountered in the practice of pediatrics today; UTIs comprise a severe problem, since renal scarring occurs in up to 20% of children with acute pyelonephritis (PN) (4, 11) and can result in an impairment of renal function. A vaccine against UTI is needed. Thorough knowledge of the immune mechanisms involved in protection would be beneficial in the development of effective vaccines.UTIs are mostly of the ascending type, and therefore, the first defense line the pathogen encounters is the local immune system on the mucosa of the urinary tract, especially urinary antibodies. It has been shown that local antibodies can bind to the infecting bacteria and prevent their adherence to mucosal surfaces (29,31,33,34) and the following infection. Accordingly, in animal experiments, local immunization eliciting local antibodies has been shown to protect against disease (36, 37). Recently, in adults, a vaginally administered vaccine has proven to be protective against reinfections in phase II trials (9, 35). If a urinary pathogen is able to cross the mucosal barrier, it must be cleared by the systemic immune mechanisms. It appears that an optimal defense state would involve both local and systemic immunity. The fact that 75% of previ...

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Section: Discussionmentioning

confidence: 95%