Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection.
BACKGROUND
Urinary tract infections (UTIs) are important causes of morbidity and death. The present study investigated whether genetic factors influence susceptibility to acute pyelonephritis (APN). CXCR1 expression was investigated as a factor predisposing to APN, because low CXCR1 expression has been associated with disease susceptibility in mice and disease-prone children.


METHODS
The families of APN-prone children (n=130) and of age-matched control subjects without UTI (n=101) were studied. Three-generation pedigrees of UTI-associated morbidity were established by means of structured interviews of the families. CXCR1 expression was quantified by flow cytometric analysis of peripheral blood neutrophils obtained from family members and control subjects.


RESULTS
APN was significantly more common in the family members of the APN-prone children (20 [15%] of 130 family members) than in the relatives of the control subjects (3 [3%] of 101 family members) (P<.002). Acute cystitis, in contrast, occurred with equal frequency in both groups (19%; P=1.0). Some families included many affected individuals, consistent with a dominant pattern of inheritance, whereas other families showed a recessive pattern of disease susceptibility. CXCR1 expression was significantly lower in the APN-prone children and in their relatives than in pediatric and adult control subjects (P<.0001).


CONCLUSIONS
Our results suggest that susceptibility to APN is inherited and that low CXCR1 expression might predispose to disease.
Lundstedt
Ann-Charlotte
AC
Department of Microbiology, Immunology, and Glycobiology, Lund University, Lund, S-223 62, Sweden.
Leijonhufvud
Irene
I
Ragnarsdottir
Bryndis
B
Karpman
Diana
D
Andersson
Björn
B
Svanborg
Catharina
C
D000907:Antibodies, Bacterial / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015169:Colony Count, Microbial; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D011704:Pyelonephritis / Q000235:genetics*; D023062:Receptors, Interleukin-8A / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D012008:Recurrence; D012737:Sex Factors; D014552:Urinary Tract Infections / Q000235:genetics* / Q000276:immunology; D014556:Urine / Q000382:microbiology
D000907:Antibodies, Bacterial; D023062:Receptors, Interleukin-8A