Colitis in chronic granulomatous disease

Werlin, Steven L.; Chusid, Michael J.; Caya, James G.; Oechler, Herbert W.

doi:10.1016/0016-5085(82)90023-3

Cited by 88 publications

(36 citation statements)

References 8 publications

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“…Similarly, mutations in a disintegrin and metalloprotease 17 ( ADAM17 ) are associated with early onset IBD in accordance with susceptibility to intestinal inflammation observed in mice with Adam17 deletion 17 18. Further, the study of primary immunodeficiencies (PID), such as chronic granulomatous disease (CGD), Wiskott–Aldrich syndrome, and IPEX has revealed monogenetic immune defects associated with chronic intestinal inflammation 8 19 20. These studies demonstrate how individual genetic variants can lead to intestinal inflammation and, together with functional studies in CD patients,21 22 lend support to the concept of primary immune defects underlying a subset of IBD cases 8 23 24.…”

Section: Introductionmentioning

confidence: 84%

XIAP variants in male Crohn's disease

Zeißig

Petersen

Milutinovic

et al. 2014

Gut

133

112

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Objective The genetic basis of inflammatory bowel disease (IBD) is incompletely understood. The aim of this study was to identify rare genetic variants involved in the pathogenesis of IBD. Design Exome sequencing and immunological profiling were performed in a patient with early onset Crohn's disease (CD). The coding region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was sequenced in samples of 275 paediatric IBD and 1047 adult-onset CD patients. XIAP genotyping was performed in samples of 2680 IBD patients and 2864 healthy controls. Functional effects of the variants identified were investigated in primary cells and cultured cell lines. Results Our results demonstrate the frequent occurrence of private variants in XIAP in about four percent of male patients with paediatric-onset CD. While XIAP mutations are known to be associated with the primary immunodeficiency (PID) X-linked lymphoproliferative disease type 2 (XLP2), CD patients described here exhibited intestinal inflammation in the absence of XLP2 and harboured a spectrum of mutations partially distinct from that observed in XLP2. The majority of XIAP variants identified was associated with a selective defect in NOD1/2 signalling, impaired NOD1/2-mediated activation of NF-κB, and altered NF-κB-dependent cytokine production. Conclusions This study reveals the unanticipated, frequent occurrence of XIAP variants in male paediatriconset CD. The link between XIAP and NOD1/2, and the association of XIAP variants with XLP2, support the concept of PID in a subset of IBD patients. Moreover, these studies provide a rationale for the implementation of XIAP sequencing in clinical diagnostics in male patients with severe CD.

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Section: Introductionmentioning

confidence: 84%

XIAP variants in male Crohn's disease

Zeißig

Petersen

Milutinovic

et al. 2014

Gut

133

112

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“…A hallmark of CGD is the formation of abnormal inflammatory granuloma that may result in colitis and may obstruct organ systems such as the urinary tract [38, [95][96][97]. The formation of granuloma in the absence of infectious agents may be the result of an incapability of neutrophils to digest foreign material.…”

Section: Chronic Granulomatous Disease (Cgd)mentioning

confidence: 99%

Inflammatory bowel disease: is it a primary immunodeficiency?

Glocker

Grimbacher

2011

Cell. Mol. Life Sci.

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Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn's disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system.

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“…1,2 Interestingly, up to 40% of CGD patients develop intestinal inflammation that is very similar to the colitis observed in inflammatory bowel disease (IBD) patients. [3][4][5] Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset before 6 years of age 6,7 and has increased in incidence dramatically during the past decade. 8 It primarily affects the colon, 1,2 and the disease extent and location and endoscopic and histologic appearance of the colonic inflammation often resembles the colonic disease observed in CGD.…”

mentioning

confidence: 99%