Sensitivity of Serum Tissue Transglutaminase Antibodies for Endomysial Antibody Positive and Negative Coeliac Disease

Background: Serum antibodies to tissue transglutaminase (tTGA) are reported to have high sensitivity and specificity for coeliac disease and to correlate closely with endomysial antibodies (EmA). We assessed their performance in a coeliac population with a high proportion of EmA-negative patients, who have been under-represented in previous studies. Methods: We used a commercial ELISA kit to test for IgA class tTGA in sera from a population of 73 untreated coeliac patients with normal serum IgA and a high percentage (19%) EmA-negative, taking 58 patients with normal duodenal biopsies as controls. EmA was measured using indirect immunofluorescence. Results: Forty-six (63%) patients with villous atrophy (VA) had both tTGA and EmA. However, when considered separately, sensitivities of tTGA and EmA for VA were similar (75% versus 81%) and both had high specificity (98% versus 97%). As 9 patients were tTGA-positive only and 13 had EmA only, selection of patients for biopsy on the presence of either antibody would have had a sensitivity of 93% (68 of 73), with 5 (7%) patients seronegative for both. Conclusion: Although the ELISA tTGA assay is more convenient than EmA testing, it offers no advantages in sensitivity or specificity if used in isolation. However, incomplete concordance between EmA and tTGA positivity means that combination screening with both assays offers higher sensitivity, as almost a third of patients have only one antibody. As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.     

Reliance on Serum Endomysial Antibody Testing Underestimates the True Prevalence of Coeliac Disease by One Fifth

Background: Although IgA endomysial antibody (EmA) is currently the serologic test of choice in selecting suspected coeliac patients for duodenal biopsies, false-negative cases have been reported and may be more common than previous studies suggest. We assessed the sensitivity of EmA for patients with biopsy-confirmed villous atrophy (VA). Methods: We studied 89 patients without IgA deficiency for whom biopsy had not been primarily prompted by a positive EmA result. VA was graded as partial, subtotal, or total (PVA, STVA, TVA). Serum EmA was assayed with indirect immunofluorescence. Results: The sensitivity of EmA for VA was 78% (69 of 89) and was similar for PVA (79%) and ST/TVA (77%). Only 4 of the 20 EmA-negative patients had increased serum IgA-class antigliadin antibody levels as measured with enzyme-linked immunosorbent assay. All seronegative patients who complied with dietary gluten exclusion responded clinically, with histologic improvement after 12 months in 8 (67%) of 12 patients who had follow-up biopsies. Conclusions: EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.     

Reliance on serum endomysial antibody testing underestimates the true prevalence of coeliac disease by one fifth

BACKGROUND: Although IgA endomysial antibody (EmA) is currently the serologic test of choice in selecting suspected coeliac patients for duodenal biopsies, false-negative cases have been reported and may be more common than previous studies suggest. We assessed the sensitivity of EmA for patients with biopsy-confirmed villous atrophy (VA). METHODS: We studied 89 patients without IgA deficiency for whom biopsy had not been primarily prompted by a positive EmA result. VA was graded as partial, subtotal, or total (PVA, STVA, TVA). Serum EmA was assayed with indirect immunofluorescence. RESULTS: The sensitivity of EmA for VA was 78% (69 of 89) and was similar for PVA (79%) and ST/TVA (77%). Only 4 of the 20 EmA-negative patients had increased serum IgA-class antigliadin antibody levels as measured with enzyme-linked immunosorbent assay. All seronegative patients who complied with dietary gluten exclusion responded clinically, with histologic improvement after 12 months in 8 (67%) of 12 patients who had follow-up biopsies. CONCLUSIONS: EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.     

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits

BACKGROUND: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. PATIENTS: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. RESULTS: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.     

Tissue transglutaminase antibodies in patients with end-stage heart failure

OBJECTIVE: For celiac disease (CD), screening a trend has recently emerged to measure tissue transglutaminase antibodies (tTGA) by immunoassays instead of the more laborious endomysial antibodies (EmA), as they recognize the same target, tissue transglutaminase (tTG). However, a high rate of false-positive results has been reported in some patient series with diseases known to be associated with CD. Moreover, tTG is a ubiquitous, multifunctional enzyme, overexpressed in experimental models of heart failure. Therefore, we assessed the specificity of tTGA assays in a large series of EmA-negative patients with end-stage heart failure. METHODS: We studied 288 patients with end-stage heart failure and 60 blood donors. No subject had clinical evidence of CD or IgA deficiency, and all were EmA negative. Serum IgA and IgG tTGA were measured by means of commercial kits using as substrate, either guinea pig or recombinant human tTG. Blocking studies and Western blots were also performed using recombinant human tTG. RESULTS: All blood donor sera were IgA tTGA negative. IgA tTGA positivity was observed in 47.6% and 49.1% of patients with heart failure using, respectively, guinea pig tTG and recombinant human tTG as substrates. Preincubation of positive sera with recombinant human tTG resulted in 81% blocking of IgA tTGA in immunoassay. Western blot analysis confirmed the presence of antibodies against recombinant human tTG. IgA tTGA-positive sera were also IgG tTGA positive. CONCLUSIONS: IgA and IgG tTGA occur in a large number of EmA-negative patients with end-stage heart failure, and their presence is unlikely to be caused by concomitant CD.     

Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery

OBJECTIVE: Although serum IgA-class endomysial antibody (EmA) has high sensitivity for villous atrophy (VA) in patients with untreated celiac disease, few studies have attempted to correlate EmA seroconversion with histological recovery after starting a gluten-free diet. We prospectively studied changes in EmA status and in duodenal histology of seropositive patients after dietary treatment. METHODS: Patients with VA and EmA had repeat EmA testing at 3, 6, and 12 months after starting gluten-free diet, plus assessment of dietary compliance by dietitians and follow-up duodenal biopsy at 12 months. VA before and after treatment was classified as partial (P), subtotal (ST), and total (T). RESULTS: Of 77 patients with newly diagnosed VA and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with T or STVA and 16 of 20 (80%) with PVA. Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months. However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only three (33%) of 10 patients with persisting ST or TVA and two (9%) of 22 with PVA remained EmA positive. Four of the five patients with persisting EmA had poor dietary compliance. CONCLUSIONS: EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance. Although there are no clear guidelines regarding the need for follow-up biopsy, EmA seroconversion cannot substitute. The apparent association between dietary compliance and seroconversion suggests that gluten intake may determine whether untreated celiac patients are EmA positive or negative for a given degree of small bowel damage.     

Activation of Genes for Superoxide Dismutase,Interleukin-1ß, Tumor Necrosis Factor-a,and Intercellular Adhesion Molecule-1 during Healing of Ischemia-Reperfusion-Induced Gastric Injury

The diagnostic sensitivity and specificity of IgA endomysium antibodies (EmA) and IgA gliadin antibodies (AGA) for coeliac disease (CD) were studied in Swedish children. Indirect immunofluorescence was used for demonstration of EmA and the diffusion-in-gel enzyme-linked immunosorbent assay method for AGA. Serum samples were collected and analysed from 77 consecutive children undergoing small-intestinal biopsy on recognized clinical indications. The diagnostic sensitivity for CD was 98.1% for EmA and 86.5% for AGA. The specificity of the two tests was 92.7% for EmA and 92.7% for AGA in paediatric patients. In addition, 115 sera from control children showed 2.6% positive for EmA and (1.9% positive for AGA.     

Association of coeliac disease with primary biliary cirrhosis in Poland

OBJECTIVES: In western and northern but not southern Europe, the prevalence of coeliac disease among patients with primary biliary cirrhosis (PBC) is higher than in the general population. We analysed the prevalence of coeliac disease among patients with PBC in Poland, a central European country. METHODS: In 115 patients with PBC, immunoglobulin A (IgA) antibodies against guinea-pig tissue transglutaminase (tTGA), monkey endomysium (EMA) and gliadin (AGA) were determined. In patients positive for tTGA and/or EMA, the DNA typing of HLA-DQB gene and small-bowel biopsy were performed. RESULTS: IgA EMA was found in one patient with PBC (0.9%, 95% CI 0-2.5%). tTGA was detected in seven patients (6%, 95% CI 1.8-10.3%). Small-bowel biopsy showed flat mucosa in one subject, who was EMA positive/tTGA negative/AGA negative, and normal histology in four tTGA-positive/EMA-negative patients. In the latter four patients, the positive tTGA result was caused by IgA reactivity to proteins other than transglutaminase. Prevalence of coeliac disease in our 115 patients with PBC was 0.9% (95% CI 0-1.9%). In one patient with silent coeliac disease presenting with the HLA-DQ2 allele, introduction of a gluten-free diet was followed by improvement in liver function tests, improvement in histology of the distal duodenum, and disappearance of EMA. CONCLUSIONS: Our results from Poland do not confirm a high prevalence of coeliac disease in PBC patients. Guinea-pig liver transglutaminase immunolinked assay cannot be used as a screening test for coeliac disease in PBC patients. A gluten-free diet may be helpful in restoration of liver function in patients with such an association.     

Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with Type 1 diabetes mellitus.

AIMS: To investigate the clinical significance of the determination of IgA antibodies to tissue transglutaminase (tTG) for the detection of silent coeliac disease in patients with Type 1 diabetes mellitus. METHODS: A total of 520 patients with diabetes (median age 14.2 years, range 1-27) were tested for IgA antibodies to tTG (IgA anti-tTG, ELISA), endomysium (EmA, indirect immunofluoresence) and gliadin (IgA-AGA, enzyme immunometric assay) after ruling out IgA deficiency. RESULTS: The prevalence of IgA anti-tTG among patients with diabetes was 4.4% (23 of 520), and that of EmA and IgA-AGA 3.5% (18 of 520, respectively). The coefficient of agreement between IgA anti-tTG and EmA was high (Cohen's kappa = 0.87, P < 0.001). Thirteen of the 23 IgA anti-tTG-positive patients underwent duodenal biopsy. Coeliac disease was confirmed in nine of 13 patients. One of them was negative for EmA and AGA, but positive for IgA anti-tTG. Retrospective annual determinations up to 8 years in six IgA anti-tTG-positive patients showed both permanent and transient elevations of the serological markers. CONCLUSIONS: These data show that a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.     

Impact of mass screening for gluten-sensitive enteropathy in working population

AIM： TO assess： （1） frequency and clinical relevance of gluten sensitive enteropathy （GSE） detected by serology in a mass screening program; （2） sensitivity of antitransglutaminase （tTGA） and antiendomysium antibodies （EmA）; and （3） adherence to gluten-free diet （GFD） and follow-up.
METHODS： One thousand, eight hundred and sixty-eight subjects recruited from an occupational health department underwent analysis for tTGA and EmA and, if positive, duodenal biopsy, DQ2/DQ8 genotyping, clinical feature recording, blood tests, and densitometry were performed. Since 〉 98% of individuals had tTGA 〈 2 U/mL, this value was established as the cut-off limit of normality and was considered positive when confirmed twice in the same sample. Adherence to a GFD and follow up were registered.
RESULTS： Twenty-six （1.39%） subjects had positive tTGA and/or EmA, and 21 underwent biopsy： six Marsh Ⅲ （one Ⅲa, four Ⅲb, one Ⅲc）, nine Marsh Ⅰ and six Marsh 0 （frequency of GSE 1：125）. The sensitivity of EmA for GSE was 46.6% （11.1% for Marsh Ⅰ, 100% for Marsh Ⅲ）, while for tTGA, it was 93.3% （88.8% for Marsh Ⅰ, 100% for Marsh Ⅲ）. All 15 patients with abnormal histology had clinical features related to GSE. Marsh Ⅰ and Ⅲ subjects had more abdominal pain than Marsh 0 （P = 0.029）, and a similar trend was observed for distension and diarrhea. No differences in the percentage of osteopenia were found between Marsh Ⅰ and Ⅲ （P = 0.608）. Adherence to follow-up was 69.2%. Of 15 GSE patients, 66.7% followed a GFD with 80% responding to it.
CONCLUSION： GSE in the general population is frequent and clinically relevant, irrespective of histological severity, tTGA is the marker of choice. Mass screening programs are useful in identifying patients who can benefit from GFD and follow-up.     

Coeliac disease in patients with autoimmune thyroiditis

BACKGROUND AND AIMS: The close association between coeliac disease and autoimmunity prompted us to perform an antibody screening for gluten-sensitive enteropathy in patients with autoimmune thyroid dysfunction. METHODS: Sera from 220 patients with autoimmune thyroiditis, 50 euthyroid subjects with thyroid nodules and 250 blood donors were tested for IgA anti-tissue transglutaminase (anti-tTG) and antiendomysial antibodies (EmA). RESULTS: IgA anti-tTG was positive in 7 patients with autoimmune thyroiditis, whereas IgA EmA was found only in 6 of them. Duodenal biopsy confirmed coeliac disease diagnosis disclosing marked and mild villous atrophy in 6 and 1 of them, respectively. All but 2 of the 7 coeliacs did not show any sign of malabsorption. All euthyroid controls were negative for IgA antibodies, whereas 1 blood donor, positive for both IgA anti-tTG and EmA, was found to be coeliac. The prevalence of coeliac disease in patients with autoimmune thyroiditis (3.2%) was significantly higher than that found in blood donors (0.4%) (p = 0.022, Fisher's exact test). CONCLUSIONS: Antibody screening for coeliac disease should be included in the work-up of patients with autoimmune thyroiditis. Either IgA anti-tTG or EmA may be used, even though the former seems to be slightly more sensitive than the latter.     

Predictive value of serological tests in the diagnosis of celiac disease

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.     

Histology of the terminal ileum in coeliac disease

Background: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten‐sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. Methods: Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). Results: One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P?Conclusions: Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.     

Histology of the terminal ileum in coeliac disease

BACKGROUND: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten-sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. METHODS: Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). RESULTS: One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P< 0.005) in the coeliac group than among controls (mean per 100 enterocytes 26 versus 10). An ileal IEL count > or =25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%. CONCLUSIONS: Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.     

IgA Antiendomysial Antibodies on the Umbilical Cord in Diagnosing Celiac Disease Sensitivity,Specificity, and Comparative Evaluation with the Traditional Kit

Background: The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus. Methods: We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8–12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed with commercially available kits; the slides with umbilical cord were prepared in our laboratory. Results: There was a perfect concordance between EmA results evaluated on umbilical cord and those on monkey esophagus; there was a doubtful result in only one case on human umbilical cord, which was positive with low liter on monkey esophagus. EmA specificity was 100%; the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90% and 100% depending on whether controls without gastrointestinal disorders or patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG and AGA IgA. Conclusions: Using human umbilical cord as a substrate for EmA may provide the same sensitivity and specificity as offered by the test using monkey esophagus substrate, thus reducing costs and avoiding the use of endangered species.     

Comparison of IgA endomysium antibody and IgA tissue transglutaminase antibody in celiac disease.

The antigen for immunoglobulin (Ig) A endomysium antibody (EmA), a sensitive and specific serological marker for celiac disease, has recently been described as tissue transglutaminase (tTG). The aim of this study was to compare the assays used to measure IgA EmA and IgA tTG antibody in patients with celiac disease and disease control subjects. Sera from 21 patients with untreated celiac disease, 48 patients with treated celiac disease and 128 disease control subjects were tested both for IgA EmA with the use of indirect immunofluorescence against human umbilical cord and for IgA tTG antibody with the use of ELISA. Titres of IgA tTG antibody were significantly higher in both the untreated and treated celiac groups than in the disease control group. Titres in the treated group were, however, significantly lower than in the untreated group. A reference range was calculated to include 99.8% of the disease control group in whom small bowel biopsy showed no evidence of celiac disease. One patient from the disease control group with raised IgA tTG antibody titres and positive IgA EmA was found to have celiac disease on small bowel biopsy. The sensitivity, specificity, and positive and negative predictive values of the IgA EmA assay were all 100%. The sensitivity of the IgA tTG antibody assay was 95%, specificity 100%, positive predictive value 100% and negative predictive value 97.7%. An ELISA used to measure IgA tTG antibody is an excellent tool to screen for celiac disease and may prove useful for monitoring response to treatment.     

The natural history of gluten sensitivity: report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives

OBJECTIVE: Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment. METHODS: After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.     

Anti-transglutaminase antibodies and coeliac disease

Background: Anti-endomysial antibodies have high specificity for coeliac disease but measurements are limited by the requirement for monkey oesophagus, a substrate that is expensive, and of limited availability and ethical acceptance. Tissue transglutaminase has recently been identified as the endomysial autoantigen in coeliac disease.
Aims: To examine the validity of serum tissue transglutaminase antibody levels in patients with coeliac disease and to assess their sensitivity and specificity against standard serological tests.
Methods: Serum IgA anti-tissue transglutaminase antibody titres (measured by ELISA), IgA anti-gliadin antibody litres (measured by a commercial ELISA) and anti-endomysial antibody titres (measured by indirect immunofluorescence) were determined in 46 untreated and 14 treated patients biopsy-proven coeliac disease and 145 disease and healthy controls.
Results: All patients with untreated coeliac disease were positive for anti-endomysial and anti-tissue transglutaminase antibodies (sensitivity 100%). Seventy-one per cent of treated coeliac patients were anti-tissue transglutaminase antibody negative. Five of 145 disease and healthy controls had low titres of anti-tissue transglutaminase antibody (specificity 97%); no controls were anti-endomysial antibody positive.
Conclusions: Our results demonstrated the sensitivity and specificity of IgA anti-tissue transglutaminase antibodies to correlate highly with anti-endomysial antibodies in the diagnosis of coeliac disease. The ELISA for IgA anti-tissue transglutaminase antibodies is quantitative and easy to perform and is a valid alternative to indirect immunofluorescence for anti-endomysial antibodies in screening for suspected coeliac disease.     

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.