Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease
Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease
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DOI：
10.1023/a:1005541700805
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发表时间：
2000-06-01
影响因子：
3.1
通讯作者：
Dieckgraefe, BK
中科院分区：
文献类型：
--
作者：
Korzenik, JR;Dieckgraefe, BK
目前关于克罗恩病病因的假说提出了过度的免疫反应，主要是t细胞驱动的，可能是针对内源性细菌的。因此，标准疗法的目的是抑制这种免疫反应。另一种致病理论解释了迄今为止尚未得到重视的流行病学和病理生理学观察结果，即：(1)中性粒细胞功能缺陷的遗传性疾病可引起与克罗恩病难以区分的临床和病理综合征；(2)中性粒细胞功能异常在克罗恩病中有很好的描述；(3)与其他慢性炎性疾病有关的一组细菌导致中性粒细胞功能受损；(4) 20世纪克罗恩病的环境危险因素可能直接抑制中性粒细胞功能，并可能导致优势肠道菌群的转变，产生类似的效果。我们认为，一些克罗恩病病例是由于环境和遗传影响的相互作用导致粘膜中性粒细胞功能受损，导致不能有效清除粘膜内微生物。在包含现有数据的同时，这一假设提出了粘膜免疫反应的近似缺陷。如果这种模式是正确的，新的治疗方法可能包括改变肠道菌群和刺激中性粒细胞功能的策略。
The current hypothesis for the etiology of Crohn's disease proposes an excessive immune response, largely T-cell driven, possibly against endogenous bacteria. Standard therapy is therefore directed towards suppression of this immune response. An alternative theory of pathogenesis accounts for epidemiologic and pathophysiologic observations that have been hitherto underemphasized, namely, (1) genetic disorders with deficiencies in neutrophil function can give rise to a clinical and pathologic syndrome indistinguishable from Crohn's; (2) abnormal neutrophil function is well described in Crohn's disease; (3) a group of bacteria implicated in other chronic inflammatory disorders causes impairment of neutrophil function; and (4) 20th century environmental risk factors for Crohn's disease may directly suppress neutrophil function and may have led to a shift in the dominant gut flora with similar effects. We propose that some cases of Crohn's disease result from the interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in failure to effectively clear intramucosal microbes effectively. While encompassing existing data, this hypothesis proposes a proximate defect in the mucosal immune response. If this paradigm were correct, new therapeutic approaches might involve strategies to alter intestinal flora and stimulate neutrophil function.