title: Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies.
abstract: BACKGROUND
  Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut.
  
  
  METHODS
  Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age.
  
  
  RESULTS
  There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014).
  
  
  CONCLUSIONS
  Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.
authors.affiliation: Centre for Infectious Diseases, University of Edinburgh, King's Buildings, Edinburgh EH9 3JF, UK. s0231156@sms.ed.ac.uk
authors.forename: Suzanne G
authors.initials: SG
authors.lastname: St Rose
authors.forename: Nora
authors.initials: N
authors.lastname: Hunter
authors.forename: Louise
authors.initials: L
authors.lastname: Matthews
authors.forename: James D
authors.initials: JD
authors.lastname: Foster
authors.forename: Margo E
authors.initials: ME
authors.lastname: Chase-Topping
authors.forename: Loeske E B
authors.initials: LE
authors.lastname: Kruuk
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Shaw
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rhind
authors.forename: Robert G
authors.initials: RG
authors.lastname: Will
authors.forename: Mark E J
authors.initials: ME
authors.lastname: Woolhouse
mesh_terms: D017677:Age Distribution; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000635:transmission; D004198:Disease Susceptibility; D006801:Humans; D010581:Peyer's Patches / Q000033:anatomy & histology / Q000502:physiology*; D017096:Prion Diseases / Q000635:transmission*; D012307:Risk Factors; D012756:Sheep; D012757:Sheep Diseases / Q000635:transmission; D013045:Species Specificity