title: Exposure to hookworms in patients with Crohn's disease: a case-control study.
abstract: BACKGROUND
  Helminths have been used to inhibit intestinal inflammation in patients with Crohn's disease.
  
  
  OBJECTIVE
  This study was undertaken to determine if there is a protective association of prior hookworm infection with Crohn's disease, in a region where there is epidemiological transition from parasitic and infectious diseases to increased auto-inflammatory diseases.
  
  
  METHODS
  Hookworm exposure was assessed by peripheral blood mononuclear cell (PBMC) activation by hookworm antigens in 78 patients with Crohn's disease and 75 healthy control participants. The change in proportion of T cells exhibiting CD69 after exposure to crude hookworm antigens was measured. Interferon-γ ELISPOT response to a panel of six recombinant hookworm antigens was analysed.
  
  
  RESULTS
  Patients with Crohn's disease were more often from an urban background (P=0.005) compared to controls, while their socioeconomic status was not significantly different. T cell activation (increase in CD3(+) CD69(+) population) by hookworm antigen was significantly higher in controls compared to Crohn's disease patients (P=0.017), while activation by the nonspecific mitogen phytohemagglutinin was similar in both groups. Circulating T memory cells (CD3(+) CD45RO(+)) after exposure to hookworm antigens were not significantly different between the two groups. Mirroring these changes, interferon-γ ELISPOT responses to hookworm antigens were seen in 36 of 75 controls compared to 20 of 78 Crohn's disease patients (Fisher's exact P=0.005). Multivariate analysis indicated that CD3CD69 shifts (P=0.019), ELISPOT reactivity (P=0.039) and place of residence (P=0.024) were all independently associated with Crohn's disease.
  
  
  CONCLUSIONS
  The inverse association between Crohn's disease and hookworm antigen reactivity is consistent with the hygiene hypothesis, but requires further exploration.
authors.affiliation: Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
authors.forename: J
authors.initials: J
authors.lastname: Kabeerdoss
authors.forename: S
authors.initials: S
authors.lastname: Pugazhendhi
authors.forename: V
authors.initials: V
authors.lastname: Subramanian
authors.forename: H J
authors.initials: HJ
authors.lastname: Binder
authors.forename: B S
authors.initials: BS
authors.lastname: Ramakrishna
mesh_terms: D000293:Adolescent; D000328:Adult; D000723:Ancylostomatoidea / Q000276:immunology*; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000276:immunology*; D005260:Female; D006725:Hookworm Infections / Q000276:immunology*; D006801:Humans; D061148:Hygiene Hypothesis; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008213:Lymphocyte Activation; D008297:Male; D012307:Risk Factors; D012423:Rural Health; D012959:Socioeconomic Factors; D013601:T-Lymphocytes / Q000276:immunology*; D014504:Urban Health; D055815:Young Adult
chemical_list: D000947:Antigens, Helminth