Celiac disease: pathogenesis of a model immunogenetic disease

Kagnoff, Martin F.

doi:10.1172/jci30253

Cited by 333 publications

(280 citation statements)

References 97 publications

(100 reference statements)

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“…The prevalence of CD exhibits an iceberg effect; the number of asymptomatic cases with positive serology and biopsy is 5-to 7-fold higher than typical symptomatic individuals exhibiting signs and symptoms including abdominal pain, growth retardation, short stature, chronic diarrhea, iron deficiency anemia that is refractive to treatment and intestinal lymphoma (6,12,21,29) . Serologic tests such as the anti-endomysium IgA antibody test (EMA), the anti-tissue transglutaminase immunoglobulin (Ig) A antibody test (anti-tTG Ab) and HLA DQ2 or DQ8 genotype testing are useful for evaluation of asymptomatic subjects as well as patients with diabetes mellitus, thyroiditis, Down syndrome, Turner syndrome, William syndrome, IgA deficiency and first-degree relatives of patients with CD (1,4,5,17) . It is therefore logical to screen these populations for other autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of celiac disease in siblings of Iranian patients with celiac disease

Chomeili¹,

Aminzadeh²,

Hardani³

et al. 2011

Arq. Gastroenterol.

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-Context -Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. Objective -To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. Methods -Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. Results -A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3% of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. Conclusion -High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.

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Section: Introductionmentioning

confidence: 99%

Prevalence of celiac disease in siblings of Iranian patients with celiac disease

Chomeili¹,

Aminzadeh²,

Hardani³

et al. 2011

Arq. Gastroenterol.

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“…9 However, accumulating evidence suggests that celiac patients may suffer from gluten-sensitive symptoms even before villous atrophy has developed, [10][11][12][13] and an increased risk of osteoporosis has been reported also for this group of patients. 10 In a recent work, Bertini et al have examined a cohort of CD patients, before and after gluten free diet GDF, and healthy controls, by 1 H NMR metabolic profiling of their serum and urine samples. 14 Through multivariate analysis, they were able to demonstrate the existence of a clear metabonomic 15 signa-ture of CD and to identify a number of serum and urine metabolites whose levels were significantly different in CD at diagnosis as compared to controls.…”

Section: Introductionmentioning

confidence: 99%

Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics

et al. 2010

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Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an early stage and its treatment with a gluten-free diet (GFD) are important for optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic approach, we have shown that CD has a well-defined metabonomic signature. Here we address potential CD patients, defined as subjects who do not have, and have never had, a jejunal biopsy consistent with clear CD, and yet have immunological abnormalities similar to those found in celiac patients. Sixty-one overt CD patients at diagnosis, 29 patients with potential CD, and 51 control subjects were examined by 1 H NMR of their serum and urine: out of 29 potential CD patients, 24 were classified as CD and 5 as control subjects. Potential CD largely shares the metabonomic signature of overt CD. Most metabolites found to be significantly different between control and CD subjects were also altered in potential CD. Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of GFD in patients with potential CD, as recently suggested by prospective clinical studies.

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“…Early associations based on serological typing were established for multiple sclerosis, 3,4 type I diabetes 5,6 and celiac disease 7,8 which were subsequently resolved to specific human leukocyte antigen (HLA)-DR/DQ haplotypes. 9,10 Moreover, recent genomewide association studies using common single nucleotide polymorphism (SNP) markers have served to underline the remarkable contribution of this region in susceptibility to autoimmune disease, 11 which dwarfs any other genetic effect. Although the functional basis for the observed class II associations in autoimmune disease remain incompletely understood, one long held view suggests a breakdown in immunological tolerance to self-antigens through presentation of peptides to autoreactive T cells.…”

Section: Introductionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

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Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

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Celiac disease: pathogenesis of a model immunogenetic disease

Cited by 333 publications

References 97 publications

Prevalence of celiac disease in siblings of Iranian patients with celiac disease

Prevalence of celiac disease in siblings of Iranian patients with celiac disease

Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

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