Potential Celiac Patients: A Model of Celiac Disease Pathogenesis

Maria Pia Sperandeo; Antonella Tosco; Valentina Izzo; Francesca Tucci; Riccardo Troncone; Renata Auricchio; Jihane Romanos; Gosia Trynka; Salvatore Auricchio; Bana Jabri; Luigi Greco

doi:10.1371/journal.pone.0021281

Potential Celiac Patients: A Model of Celiac Disease Pathogenesis

Maria Pia Sperandeo^*, Antonella Tosco, Valentina Izzo, Francesca Tucci, Riccardo Troncone, Renata Auricchio, Jihane Romanos, Gosia Trynka, Salvatore Auricchio, Bana Jabri, Luigi Greco

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background and Aim: Potential celiacs have the 'celiactype' HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.

Methods: 127 'potential' CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of 'candidate genes' and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies.

Results: Potential CD bear a lighter HLA-related risk, compared to celiac (chi(2) = 48.42; p value = 1x10(-8)). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (chi(2) = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: chi(2) = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed.

Conclusions: Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals.

Original language	English
Article number	21281
Number of pages	8
Journal	PLoS ONE
Volume	6
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0021281
Publication status	Published - 8-Jul-2011

Keywords

NF-KAPPA-B
GENE-EXPRESSION
RISK VARIANTS
HLA
INFLAMMATION
CONTRIBUTES
ACTIVATION
MUCOSA
CELLS
IL-21

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title = "Potential Celiac Patients: A Model of Celiac Disease Pathogenesis",

abstract = "Background and Aim: Potential celiacs have the 'celiactype' HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.Methods: 127 'potential' CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of 'candidate genes' and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies.Results: Potential CD bear a lighter HLA-related risk, compared to celiac (chi(2) = 48.42; p value = 1x10(-8)). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (chi(2) = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: chi(2) = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed.Conclusions: Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals.",

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author = "Sperandeo, {Maria Pia} and Antonella Tosco and Valentina Izzo and Francesca Tucci and Riccardo Troncone and Renata Auricchio and Jihane Romanos and Gosia Trynka and Salvatore Auricchio and Bana Jabri and Luigi Greco",

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doi = "10.1371/journal.pone.0021281",

language = "English",

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T1 - Potential Celiac Patients

T2 - A Model of Celiac Disease Pathogenesis

AU - Sperandeo, Maria Pia

AU - Tosco, Antonella

AU - Izzo, Valentina

AU - Tucci, Francesca

AU - Troncone, Riccardo

AU - Auricchio, Renata

AU - Romanos, Jihane

AU - Trynka, Gosia

AU - Auricchio, Salvatore

AU - Jabri, Bana

AU - Greco, Luigi

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N2 - Background and Aim: Potential celiacs have the 'celiactype' HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.Methods: 127 'potential' CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of 'candidate genes' and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies.Results: Potential CD bear a lighter HLA-related risk, compared to celiac (chi(2) = 48.42; p value = 1x10(-8)). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (chi(2) = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: chi(2) = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed.Conclusions: Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals.

AB - Background and Aim: Potential celiacs have the 'celiactype' HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals.Methods: 127 'potential' CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of 'candidate genes' and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies.Results: Potential CD bear a lighter HLA-related risk, compared to celiac (chi(2) = 48.42; p value = 1x10(-8)). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (chi(2) = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: chi(2) = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed.Conclusions: Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals.

KW - NF-KAPPA-B

KW - GENE-EXPRESSION

KW - RISK VARIANTS

KW - HLA

KW - INFLAMMATION

KW - CONTRIBUTES

KW - ACTIVATION

KW - MUCOSA

KW - CELLS

KW - IL-21

U2 - 10.1371/journal.pone.0021281

DO - 10.1371/journal.pone.0021281

M3 - Article

SN - 1932-6203

VL - 6

JO - PLoS ONE

JF - PLoS ONE

IS - 7

M1 - 21281

ER -

Potential Celiac Patients: A Model of Celiac Disease Pathogenesis

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Keywords

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