Journal
PLOS ONE
Volume 2, Issue 9, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0000825
Keywords
-
Categories
Funding
- Swedish Medical Research Council [-07934, 14577, 14578]
- The Royal Physiographic Society
- The Medical Faculty, Lund University
- Foundation for Strategic Research
- Beijer Foundation
- Bristol-Myers Squibb
- Swedish Medical Research Council
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available