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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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | e825-(10 s) |
| Journal | PLoS ONE |
| Volume | 2 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2007 |
Subject classification (UKÄ)
- Microbiology in the medical area
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Dive into the research topics of 'A genetic basis of susceptibility to acute pyelonephritis.'. Together they form a unique fingerprint.Research output
- 1 Doctoral Thesis (compilation)
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Influence of host genetics on innate immunity and susceptibility to urinary tract infection
Ragnarsdottir, B., 2009, Department of Microbiology, Immunology and Glycobiology, Lund University. 136 p.Research output: Thesis › Doctoral Thesis (compilation)