Juan C. Gomez

Prevalence of celiac disease in argentina: screening of an adult population in the La Plata area

OBJECTIVES:Up to now, the epidemiological characteristic of celiac disease among adults in South America remains unknown. The present prospective screening was designed to determine the prevalence of celiac disease in adults from the general population in an urban area of Argentina.METHODS:Between January, 1998, and May, 2000, all couples attending a centralized laboratory for an obligatory prenuptial examination in the La Plata area were offered participation in a screening program for celiac disease. The study included 2000 subjects (996 women; median age 29 yr, range 16–79 yr). All individuals completed a clinical questionnaire at the time that serum samples were obtained. A three-step screening protocol was used, as follows: 1) all samples were tested for antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA positive were tested for antiendomysial antibody (EmA type IgA); samples that were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for intestinal biopsy.RESULTS:At the end of the screening we detected 10 subjects who were EmA-A positive and two others who were IgA-deficient (both were EmA-G positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two IgA-deficient subjects) had endoscopic intestinal biopsies showing the characteristic celiac histology. The remaining EmA-positive individual was considered to be affected by celiac disease. The overall prevalence assessed was 1:167 (6.0 × 1000 subjects; 95% CI = 3.1–10.5). Eight of the 12 (67%) subjects were female (1:124; 8.0 × 1000; 95% CI = 3.5–15.8) and four (33%) were male (1:251; 4.0 × 1000; 95% CI = 1.1–10.2). Although eight new patients were considered to be asymptomatic, three presented with a subclinical course and one was classically symptomatic. Only one patient had been previously diagnosed with celiac disease.CONCLUSIONS:Our screening protocol showed a very high prevalence of celiac disease for an urban area of Argentina that is ethnically similar to 90% of the general population of the country. The prevalence among women was double that for men, and the heterogeneous clinical picture of new patients showed predominance of asymptomatic cases.

Stratification of Bone Fracture Risk in Patients With Celiac Disease

BACKGROUND AND AIMS Our objective in this cross-sectional, case-control study was to gain insight into celiac osteopathy by examining a well-defined cohort of patients with a wide clinical spectrum of the disease. METHODS We studied 148 unselected celiac patients and 296 (1:2) age- and sex-matched controls diagnosed with functional gastrointestinal disorders. Based on the clinical history, 53% were classically symptomatic, 36% had subclinical celiac disease, and 11% were silent, detected by screening. The fracture information was obtained through an in-person interview using a pre-designed questionnaire. RESULTS Classically symptomatic patients had an increased number of fractures in the peripheral skeleton (47%) compared with age- and sex-matched controls (15%; odds ratio, 5.2; 95% confidence interval, 2.8-9.8). However, fractures in subclinical/silent celiac cases (20%) were no different from those in controls (14%; odds ratio, 1.7, 0.7-4.4). Compared with the subclinical/silent group, a significantly greater prevalence of fractures was detected in classically symptomatic patients (odds ratio, 3.6, 1.7-7.5). Compared with controls, celiac disease patients had significantly more fractures produced by mild trauma (P < 0.01), but there were no differences in the severity of trauma events that induced fractures. Mean bone density femoral neck z score was higher for subclinical/silent cases compared with classically symptomatic patients (P < 0.05). CONCLUSIONS Celiac patients show a very wide variation in fracture risk, with increased risk in classically symptomatic patients. Diagnostic and therapeutic strategies to prevent bone loss and fracture should be preferentially used in the subgroup of patients with classic clinical disease.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study.

OBJECTIVE:Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the same community-based population.METHODS:We screened 1000 consecutive subjects (497 women, age range 16–71 yr) attending a centralized laboratory for obligatory prenuptial blood tests. Serum samples obtained from all subjects were processed using two different protocols: 1) a three-level classic screening consisting of the parallel use of IgG and IgA antigliadin antibodies as first level, followed by endomysial antibodies and total serum IgA for positive patients, and finally, intestinal biopsy of positive patients; and 2) a study screening protocol consisting of the parallel use of a commercial guinea pig antitissue transglutaminase antibody and total serum IgA as first line, endomysial antibodies (type IgA and/or IgG) for positive patients, and finally, intestinal biopsy.RESULTS:The classic screening protocol identified five subjects who were eligible for intestinal biopsy, which confirmed the presence of CD in all (prevalence 5.0 × 1000, 95% CI = 1.6–11.6). Using the study algorithm, we detected seven new patients including the five patients detected by the first protocol (prevalence 7.0 × 1000, 95% CI = 2.8–14.4). The two additional patients diagnosed using the proposed algorithm had positive IgG antigliadin antibodies and normal total serum IgA and were not detected by the classic protocol. Both patients were endomysial antibodies positive. The comparative analysis showed that the classic approach was more expensive (U.S.

Tissue transglutaminase antibodies in celiac disease: assessment of a commercial kit

4687 per new patient detected) compared with the proposed study algorithm (U.S.

Risk of fracture in celiac disease: Gender, dietary compliance, or both?

3006).CONCLUSIONS:Our data showed that a new screening protocol using antitissue transglutaminase as first line followed by endomysial antibodies is a cost-effective screening and yielded more realistic figures of prevalence for CD in a community setting than the classic three-level sequential evaluation using antigliadin antibodies.

High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis

OBJECTIVE:Tissue transglutaminase was identified as the autoantigen eliciting endomysial antibody. A homemade enzyme-linked immunosorbent assay (ELISA)-based test was recently developed to determine quantitative titers of IgA antitissue transglutaminase antibody. Our objective in this study was to assess the suitability of a newly developed commercial kit for quantitative determination of antibody in patients with untreated celiac disease.MATERIALS:We tested serum samples from 79 untreated celiac patients, 42 healthy blood donors, and 18 patients with nonceliac intestinal disorders evaluated in two different centers. Samples were tested for antitissue transglutaminase, and antiendomysial and antigliadin antibodies in the center where diagnosis was performed. To assess interlaboratory variability of methods, 24 samples randomly selected were blindly tested in both centers. Antitissue transglutaminase antibodies were determined using a commercial kit (INOVA Diagnostics, Inc., San Diego, CA).RESULTS:Untreated celiac patients had significantly higher titers of antitissue transglutaminase than healthy and disease controls (p < 0.00001). According to the cut-off provided by the manufacturers (20 AU/mL), overall sensitivity was 92% (85% for one center and 100% for the other) and specificity was 98% (100% and 95%, respectively). Antiendomysial antibody was 86% sensitive and 100% specific. Discordance between antitissue transglutaminase and antiendomysial antibodies was detected in 13% of patients. Although two antitissue transglutaminase-negative cases had a positive antiendomysial antibody, the inverse situation was found in eight cases. A blind determination of antitissue transglutaminase on the same samples evidenced a good agreement (κ statistic: 0.66) between both centers when assessment was qualitative (based on the decision of positive or negative). Although correlation of titers for both determinations was highly significant (r: 0.902, p < 0.00001), a very wide interlaboratory variability (median: 50%) was detected when absolute values were considered.CONCLUSIONS:The quantitative determination of antitissue transglutaminase using a commercial kit was highly sensitive and specific for detection of celiac disease. We observed an incomplete overlapping with antiendomysial antibody. The very high variability of values between laboratories still remains to be solved so as to propose the commercial ELISA assay for the screening of celiac disease.

Telomere Length Study in Celiac Disease

AIM To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture risk. METHODS We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age- and sex-matched controls who had been diagnosed with functional gastrointestinal disorders. Data were collected through in-person interviews with an investigator. The overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis). RESULTS Compared with the control group, the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR): 1.78, 95% CI: 1.23-2.56, P < 0.002] and in men (HR: 2.67, 95% CI: 1.37-5.22, P < 0.004). Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003). In the time period after diagnosis, the risk of fractures was comparable between the CD cohort and controls in both sexes (HR: 1.08, 95% CI: 0.55-2.10 for women; HR: 1.57, 95% CI: 0.57-4.26 for men). CONCLUSION CD patients have higher prevalence of fractures in the peripheral skeleton before diagnosis. This is associated with male sex and classic clinical presentation. The fracture risk was reduced after the treatment.

Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis.

OBJECTIVE:Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer.METHODS:Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE).RESULTS:Mean frequencies of TAS and CA were significantly increased in UC patients compared to controls (p < 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized. Seven nonrandom bands significantly affected in UC patients were found (p < 0.004), showing a significant correlation with the location of cancer breakpoints (p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis showed higher levels in patients compared to controls (p < 0.006), but no differences were observed in cell cycle kinetics.CONCLUSIONS:Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.

Increased rDNA transcriptional activity in celiac disease

OBJECTIVES:Telomeres are important structures that are critical for maintaining chromosomal integrity and cell surveillance. The aim of this study was to analyze telomere length in patients with celiac disease (CD), a multifactorial disorder with a strong genetic component that exhibits genomic instability and cancer predisposition, particularly T-cell lymphomas.METHODS:Telomere length measured by telomere restriction fragments (TRF) was studied in small intestinal biopsy (SIB) samples and peripheral blood lymphocytes (PBL) from 20 untreated CD patients, distributed according to the clinical form as four asymptomatic, five monosymptomatic, and 11 polysymptomatic individuals. We also analyzed TRF from normal peripheral blood lymphocytes and normal biopsy samples as normal controls.RESULTS:TRF evaluation showed a significant telomere shortening in SIB samples from CD patients (4.21 ± 0.29 Kb) compared to PBL from the same individuals (9.17 ± 0.35 Kb) (p < 0.0001), independently of clinical form. Mean TRF peak values from normal biopsy samples were significantly higher (8.33 ± 0.38 Kb) than those observed in CD biopsy samples (p < 0.001). No differences between TRF values in CD-PBL and normal peripheral blood lymphocytes (8.89 ± 0.37Kb) were found.CONCLUSIONS:Our findings in patients with CD, a disorder in which the gluten-induced mucosal injury could accelerate telomere shortening, would increase the process of end-to-end fusions resulting in chromosomal changes, supports the hypothesis that genomic instability and telomere reduction may play a role in the cancer predisposition observed in these patients.