Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Aliment Pharmacol Ther. 2011 Oct;34(8):923-30. doi: 10.1111/j.1365-2036.2011.04824.x. Epub 2011 Aug 17.
Helminths have been used to inhibit intestinal inflammation in patients with Crohn's disease.
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.
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.
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.
The inverse association between Crohn's disease and hookworm antigen reactivity is consistent with the hygiene hypothesis, but requires further exploration.
蠕虫已被用于抑制克罗恩病患者的肠道炎症。
本研究旨在确定在寄生虫和传染病向自身炎症性疾病增加的流行病学转变的地区，先前钩虫感染与克罗恩病之间是否存在保护性关联。
通过钩虫抗原对 78 例克罗恩病患者和 75 名健康对照者的外周血单核细胞（PBMC）进行激活，评估钩虫暴露情况。测量暴露于粗钩虫抗原后表现出 CD69 的 T 细胞比例的变化。分析对六重组钩虫抗原的干扰素-γ ELISPOT 反应。
与对照组相比，克罗恩病患者更常来自城市背景（P=0.005），而其社会经济地位没有显著差异。与克罗恩病患者相比，对照组的钩虫抗原 T 细胞激活（增加 CD3+CD69+人群）明显更高（P=0.017），而两组的非特异性丝裂原植物血凝素的激活相似。暴露于钩虫抗原后循环 T 记忆细胞（CD3+CD45RO+）在两组之间没有明显差异。与这些变化相呼应，在 75 名对照者中有 36 名对钩虫抗原产生干扰素-γ ELISPOT 反应，而在 78 名克罗恩病患者中有 20 名（Fisher 确切概率 P=0.005）。多变量分析表明，CD3CD69 转移（P=0.019），ELISPOT 反应性（P=0.039）和居住地（P=0.024）均与克罗恩病独立相关。
克罗恩病与钩虫抗原反应之间的反比关系与卫生假说一致，但需要进一步探索。
