Serologic and Genetic Markers of Celiac Disease: A Sequential Study in the Screening of First Degree Relatives

Department of Pediatrics, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy.
Journal of Pediatric Gastroenterology and Nutrition (Impact Factor: 2.87). 01/2006; 42(2):150-154. DOI: 10.1097/01.mpg.0000189337.08139.83

ABSTRACT Objectives: The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy.
Methods: We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy.
Results: TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up.
Conclusions: On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Coeliac disease (CD) is a highly prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins in genetically susceptible individuals. The CD is associated with human leucocyte antigen (HLA) genes particularly with HLA-DQ alleles encoding HLA-DQ2 and DQ8 proteins. To define risk and severity alleles for CD, a total of 120 definite CD patients and 100 healthy controls were genotyped for HLA-DQB1 gene. HLA-DQB1 genotyping was performed in all patients and controls using PCR-SSP technique, and to evaluate the clinical relevance of testing for HLA-DQB1 and determining absolute risk of disease, prevalence-corrected positive predictive value and prevalence-corrected negative predictive value (PcPPV and PcNPV) were calculated. Our results for a first time show that DQB1*02:00 and DQB1*03:02 alleles and DQB1*02:01/03:02 genotype very significantly associated with increased risk of patients with CD, and DQB1*03:01,4 allele provides protection against CD in Iranian patients. Furthermore, the PcPPV for DQB*02:01 and 03:02 alleles in CD were 0.014 and 0.012, respectively, and the highest absolute risk presented by DQB*0201/0302 genotype (PcPPV = 0.079) and 98% of patients with CD carried DQB1*02:01/x or DQB1*03:02/x genotype. The results also clearly demonstrated that the DQB1*02:01 allele significantly associated with severity of CD, while DQB1*03:02 allele associated with mild form of CD. These results suggest that clinically suspected individuals for CD and first-degree relatives of patients with CD to be screened for HLA-DQB*0201 and DQB*0302 alleles for possible early diagnosis and treatments.
    International Journal of Immunogenetics 06/2014; 41(4). DOI:10.1111/iji.12128 · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of dyspepsia is up to 40% in popula-tion-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by def-ecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastroin-testinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individu-als with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic tech-niques, such as "water immersion" and confocal en-domicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically sig-nificant way. However this assumption should be con-firmed further larger studies. Core tip: Dyspepsia is classified as a chronic abdomi-nal pain-related functional disorder that affects almost 40% of the population. It can be also a manifestation of celiac disease, an immuno-mediated enteropathy, caused by the ingestion of gluten in genetically predis-posed patients. The prevalence of celiac disease among dyspeptic patients has been investigated, with results ranging from 0.5% to 2%. Celiac disease diagnosis requires histological evaluation of villous atrophy on duodenal biopsies specimens. Screening for celiac dis-ease in dyspeptic patients and routinely performing of biopsies during upper gastrointestinal endoscopy, may be useful as part of the diagnostic flow-chart of these patients.-tone S. Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy. World J Methodol 2014; 4(3): 189-196 Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: Serological markers of coeliac disease (CD) lack diagnostic value to identify mild histopathological lesions mainly in adults at risk of CD. The aim of this study was to evaluate the usefulness of human leukocyte antigen (HLA)-DQ2/8 genotyping, followed by duodenal biopsy for the detection of CD in adult first-degree relatives (FDRs) of patients with CD. Ninety-two adult DQ2/8 positive FDRs were consecutively included. A duodenal biopsy was offered irrespective of the serology result or associated symptoms. The clinical features, associated autoimmune diseases and biochemical parameters were recorded. Sixty-seven FDRs (mean age 34 years) underwent a duodenal biopsy. Histopathological alterations were found in 32 (48%) and showed the following stages: 12 Marsh I (18%), one Marsh II (1.5%), four Marsh IIIA (6%), five Marsh IIIB (7.5%) and 10 Marsh IIIC (15%). Positive serological markers were present in 17/67 (25%), with only one showing Marsh I and the remainder presenting some degree of duodenal atrophy (Marsh III). In addition, 33/67 (54%) had gastrointestinal symptoms, with dyspepsia being the most prevalent. The distribution of symptoms, anaemia and autoimmune disease was independent of the duodenal histopathological stage. Serology-based screening would diagnose 50% of the cases showing any degree of CD spectrum and miss 6% of the cases with mucosal atrophy. Adult FDRs of patients with CD can benefit from a screening strategy on the basis of HLA-DQ genotyping, followed by a duodenal biopsy. Gastrointestinal symptoms and lymphocytic enteritis are common findings that may benefit from a gluten-free diet.
    European journal of gastroenterology & hepatology 12/2013; 26(3). DOI:10.1097/MEG.0000000000000020 · 1.66 Impact Factor


Available from
Jun 1, 2014