A genetic basis of susceptibility to acute pyelonephritis.

Research output: Contribution to journalArticle

Abstract

Background

For unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.
Methods and Findings

We have obtained CXCR1 sequences from two, highly selected APN prone patient groups, and detected three unique mutations and two known polymorphisms with a genotype frequency of 23% and 25% compared to 7% in controls (p<0.001 and p<0.0001, respectively). When reflux was excluded, 54% of the patients had CXCR1 sequence variants. The UTI prone children expressed less CXCR1 protein than the pediatric controls (p<0.0001) and two sequence variants were shown to impair transcription.
Conclusions

The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)e825-(10 s)
JournalPLoS ONE
Volume2
Issue number9
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Total downloads

No data available

Related research output

Ragnarsdottir, B., 2009, Department of Microbiology, Immunology and Glycobiology, Lund University. 136 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)