scholarly journals Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C

2022 ◽  
Vol 7 ◽  
pp. 11
Author(s):  
Isabelle Williams ◽  
Sumeet Pandey ◽  
Wolfram Haller ◽  
Hein Q. Huynh ◽  
Alicia Chan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Disease Type ◽  
Peripheral Blood Mononuclear ◽  
Niemann Pick Disease ◽  
Blood Mononuclear Cells ◽  
Niemann Pick ◽  
Pick Disease

Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli. Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.

scholarly journals Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann–Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease

Gut ◽  
2016 ◽  
Vol 66 (6) ◽  
pp. 1060-1073 ◽  
Author(s):  
Tobias Schwerd ◽  
Sumeet Pandey ◽  
Huei-Ting Yang ◽  
Katrin Bagola ◽  
Elisabeth Jameson ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease

Niemann–Pick disease type C and Crohn's disease: A UK centre's experience with review of the literature

2013 ◽  
Vol 108 (2) ◽  
pp. S50-S51
Author(s):  
Elisabeth Jameson ◽  
Sarah Laraway ◽  
Edmund Cheesman ◽  
Jackie Imrie ◽  
Ed Wraith ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Type ◽  
Review Of The Literature ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Niemann-Pick Disease Type C and Crohn's Disease

2005 ◽  
Vol 50 (2) ◽  
pp. 80-81 ◽  
Author(s):  
LC Steven ◽  
CP Driver
Keyword(s):  
Crohn’S Disease ◽  
Chronic Disease ◽  
Crohn's Disease ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Limiting Condition ◽  
Pick Disease

A five year old girl with Neimann-Pick disease type C subsequently developed Crohn's Disease. This association has only been presented once previously in the literature. This report discusses the options for managing one chronic disease in the presence of another life limiting condition.

scholarly journals Niemann-Pick disease type C presenting as very early onset inflammatory bowel disease

2019 ◽  
Vol 12 (7) ◽  
pp. e229780 ◽  
Author(s):  
Chinenye Rebecca Dike ◽  
John Bernat ◽  
Warren Bishop ◽  
Catherine DeGeeter
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Inflammatory Bowel ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Niemann-Pick disease type C (NPC) has been reported in association with inflammatory bowel disease. In cases where colitis has been reported in association with NPC, the neurological manifestations of NPC often precede the development of colitis. We report a rare case of a child who presented at age 2 with perianal Crohn’s disease. Initial imaging studies to characterise the disease revealed an incidental finding of splenomegaly. Extensive workup for splenomegaly revealed NPC1 mutations consistent with NPC disease. He did not have any typical neurological symptoms at the time of his diagnosis. He is currently doing well on biweekly adalimumab injections for his Crohn’s disease and biweekly intrathecal injections of 2-hydroxypropyl-β-cyclodextrin (VTS-270) for the NPC.

scholarly journals The gene encoding the Wiskott-Aldrich syndrome (WAS) protein is transcriptionally repressed following stimulation of peripheral blood mononuclear cells with muramyl dipeptide.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Pattern Recognition ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Muramyl Dipeptide ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Wiskott Aldrich Syndrome ◽  
Blood Mononuclear Cells

The nucleotide-binding oligomerization domain protein 2, NOD2, is the pattern recognition receptor for muramyl dipeptide, a component of the cell wall of both gram-positive and gram-negative bacteria (1, 2). Sensing of muramyl dipeptide by NOD2 triggers signal transduction downstream of the RIP2 kinase to transcriptionally activate a diverse innate immune gene expression program (3-5). Single nucleotide variants in NOD2 are the strongest genetic risk factors for developing Crohn’s Disease (6, 7), an inflammatory bowel disease (8). By mining a published dataset (9), we found that among the genes whose expression changed most significantly in peripheral blood mononuclear cells (PBMC) stimulated with muramyl dipeptide, genome-wide, was the gene encoding the Wiskott-Aldrich syndrome (WAS) protein (10), a regulator of actin polymerization in hematopoietic cells (11). The WAS gene is mutated in patients with Wiskott-Aldrich syndrome (12), a genetic disorder characterized by thrombocytopenia, eczema, immunodeficiency and lymphoid malignancies (13), and whose symptoms include bloody diarrhea (14, 15). WAS RNA message was transcriptionally repressed following exposure of PBMC to muramyl dipeptide. These data link together a gene, that when mutated in humans leads to gastrointestinal symptoms not dissimilar to those found in patients with Crohn’s Disease, with the ligand for the gene whose product encodes the single most significant genetic variant conferring risk for development of Crohn’s Disease, and further suggest that the actin cytoskeleton may be a central target of gene expression changes effected by NOD2 pattern recognition of MDP.

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