Reduced gene expression of intestinal alpha-defensins predicts diarrhea in a cohort of African adults.
BACKGROUND
Human defensin (HD) 5 and HD6, both Paneth cell alpha-defensins, contribute to the antimicrobial barrier against intestinal infection. We have previously demonstrated that levels of both HD5 and HD6 mRNA were reduced in adults living in urban Zambia, compared with those in adults living in London. The aim of the present study was to determine, during 2 years of follow-up, whether alpha-defensin expression in Zambian adults is related to susceptibility to diarrhea.


METHODS
We analyzed intestinal biopsy samples from a longitudinal cohort study conducted in 83 Zambian adults by quantitative reverse-transcription polymerase chain reaction, Western blotting, immunohistochemistry, and in situ hybridization, and we measured the incidence of diarrhea.


RESULTS
Levels of HD5 and HD6 mRNA in Paneth cells varied between participants, over time, and seasonally and were strongly correlated with mucosal architecture. Gene expression was almost exclusively restricted to Paneth cells. The median (interquartile range) HD5 mRNA level was 6.0 (5.6-6.7) log10 transcripts/microg of total RNA among 18 participants who experienced diarrhea within 2 months after biopsy-sample collection, compared with 6.8 (6.2-7.3) log10 transcripts/microg of total RNA among 94 participants who did not (P=.006). A similar observation was made for HD6.


CONCLUSIONS
These data indicate that intestinal alpha-defensin expression is dynamic and seasonal and suggest that susceptibility to intestinal infection is related to alpha-defensin expression.
Kelly
Paul
P
Centre for Adult and Paediatric Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine, Department of Infectious and Tropical Diseases, United Kingdom. guts@coppernet.zm
Bajaj-Elliott
Mona
M
Katubulushi
Max
M
Zulu
Isaac
I
Poulsom
Richard
R
Feldman
Roger A
RA
Bevins
Charles L
CL
Dhaliwal
Winnie
W
D000328:Adult; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D003967:Diarrhea / Q000453:epidemiology* / Q000235:genetics*; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D015994:Incidence; D007421:Intestine, Small / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics; D015024:Zambia / Q000453:epidemiology; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D023084:alpha-Defensins