Genetic variants in the autophagy pathway contribute to paediatric Crohn's disease

Gut (Impact Factor: 14.66). 10/2008; 57(9):1336-7; author reply 1337. DOI: 10.1136/gut.2008.152207
Source: PubMed
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    • "Clinical trials using MSCs as cell based inflammatory bowel suppressive therapy for CD are promising [50] [51] [52] [53]. GWAS scan of nonsynonymous SNPs in CD has identified a mutation in the genes of autophagy [54] [55]. Autophagy is a cellular homeostatic process in which the cell compartments are recycled under stressful conditions. "
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    ABSTRACT: The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.
    11/2013; 2013(5411):929842. DOI:10.1155/2013/929842
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    • "In another pediatric study in the GWAS literature,82 a previously unreported susceptibility locus for pediatric-onset IBD at 20q13 and 21q22 was identified, suggesting that TNFRSF6B is the most plausible candidate within the 20q13 locus, involved in both antigen-presenting cell differentiation and lymphocyte function. Autophagy-associated genes (ATG16L1 and IRGM) were also seen in early-onset CD cases, further confirming autophagy as an important contributor in the pathogenesis of pediatric CD.83 "
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    ABSTRACT: Crohn's disease is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can occur in any area throughout the digestive tract. This life-long disease commonly presents with abdominal pain, diarrhea, vomiting, and weight loss. While the exact etiology of this disease is largely unknown, it is thought to arise from an interaction between microbial, immunological, and environmental factors in a genetically susceptible host, whereby the immune system attacks the intestine as it cross reacts against gut microbial antigens. The study of genetic variants associated with Crohn's disease has shed light on our understanding of disease pathophysiology. A large number of genetic variants identified in Crohn's disease are related to genes targeting microbial recognition and bacterial wall sensing, the most common being NOD2/CARD15 gene. This review will discuss the recent advance in our knowledge of genetic variants of this disease and how they influence the disease course and prognosis.
    The Application of Clinical Genetics 07/2013; 6:25-32. DOI:10.2147/TACG.S33966
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