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First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal Transcriptomic Signature that Might Protect them from Enterocyte Damage.

ABSTRACT: INTRODUCTION:Celiac disease (CeD) is an autoimmune enteropathy which affects approximately 0.7% of the global population. While first-degree relatives (FDR) of patients with CeD have a 7.5% risk of developing enteropathy, many remain protected. Therefore, intestinal mucosa of FDR might have protective compensatory mechanisms against immunological injury. We have explored the protective mechanisms that may be active in intestinal mucosa of FDR. METHODS:Intestinal mucosal biopsies (4-5 pieces) from treatment naïve patients with CeD (n?=?12), FDR (n?=?12) (anti-tTG negative) and controls (n?=?12) (anti-tTG negative) were obtained from each individual and subjected to microarray analysis using HT-12-v4 Human Expression BeadChips (Illumina). Differential gene expression analysis was carried out among CeD, FDR and controls; and resulting gene lists were analyzed using gene ontology and pathway enrichment tools. RESULTS:Patients with CeD, FDR and control groups displayed significant differential gene expression. Thirty seven genes were upregulated and 372 were downregulated in the intestinal mucosa of FDR in comparison to CeD and controls. Pseudogenes constituted about 18% (315/1751) of FDR differentially expressed genes, and formed "clusters" that associated uniquely with individual study groups. The three study groups segregated into distinct clusters in unsupervised (PCA) and supervised (random forests) modelling approaches. Pathways analysis revealed an emphasis on crypt-villous maintenance and immune regulation in the intestinal mucosa of FDR. CONCLUSIONS:Our analysis suggests that the intestinal mucosa of celiac FDR consist of a unique molecular phenotype that is distinct from CeD and controls. The transcriptomic landscape of FDR promotes maintenance of crypt-villous axis and modulation of immune mechanisms. These differences clearly demonstrate the existence of compensatory protective mechanisms in the FDR intestinal mucosa.

SUBMITTER: Acharya P

PROVIDER: S-EPMC6174158 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal Transcriptomic Signature that Might Protect them from Enterocyte Damage.

Acharya Pragyan P Kutum Rintu R Pandey Rajesh R Mishra Asha A Saha Rohini R Munjal Akshay A Ahuja Vineet V Mukerji Mitali M Makharia Govind K GK

Clinical and translational gastroenterology 20181008 10

<h4>Introduction</h4>Celiac disease (CeD) is an autoimmune enteropathy which affects approximately 0.7% of the global population. While first-degree relatives (FDR) of patients with CeD have a 7.5% risk of developing enteropathy, many remain protected. Therefore, intestinal mucosa of FDR might have protective compensatory mechanisms against immunological injury. We have explored the protective mechanisms that may be active in intestinal mucosa of FDR.<h4>Methods</h4>Intestinal mucosal biopsies ( ...[more]

PMID: 30293993

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Project description:Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder.To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism.Case-control comparison of neurobehavioral functions.University medical center.Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years).Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors.On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another.Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.

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First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal Transcriptomic Signature that Might Protect them from Enterocyte Damage.

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First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal Transcriptomic Signature that Might Protect them from Enterocyte Damage.

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