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.

Aim: 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.

Conclusion: The inverse association between Crohn's disease and hookworm antigen reactivity is consistent with the hygiene hypothesis, but requires further exploration.