Recombinant human tissue transglutaminase for diagnosis and follow-up of childhood coeliac disease

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects. All samples were also analyzed for anti-endomysium antibodies (EMA). The levels of IgA and IgG anti-tTG antibodies correlated with the condition of the small intestinal villous structure and the serum levels of IgA EMA. All of the 25 serum samples obtained from untreated patients contained IgA anti-tTG antibodies, and 24 of 25 also had IgA EMA. Of the serum samples from 53 control children, two had IgA anti-tTG antibodies and two had IgA EMA. Children younger than 5 y of age with untreated celiac disease had the highest serum levels of both IgA and IgG anti-tTG. There was already an increase in IgA anti-tTG antibodies after 2 wk of gluten challenge (p < 0.01). Although the criteria-based diagnosis of childhood celiac disease still depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides useful complementary diagnostic information. The human recombinant tTG-based ELISA can be used as a sensitive and specific test to support the diagnosis and may also be used in the follow-up of treatment in childhood celiac disease.     

Antiendomysium antibodies and coeliac disease: solved and unsolved questions. An Italian multicentre study

A total of 3783 subjects were enrolled to compare IgA and IgG gliadin antibodies (AGA) with IgA endomysium antibodies (EMA) in coeliac disease (CD). Among 688 children with untreated CD EM A were positive in 93.8%, IgA AGA in 84.9% and IgG AGA in 90.2%. AGA, but not EMA, sensitivity decreased with age. EMA were present in 3.8% of control subjects, IgA AGA in 14.9% and IgG AGA in 34.3%. Follow-up of 5 of 39 EMA-positive controls showed flat mucosa. Combined determination of EMA and AGA showed an increased predictive value: if EMA and AGA were both positive, the mucosa was flat in 99.1%, if both were negative, the mucosa was normal in 99.1%. After a gluten-free diet (GFD), IgA-AGA disappeared first. Among 21 patients not on a strict GFD and in 194 coeliac patients after challenge, EMA, but not AGA, were always positive. Among 67 first-degree relatives of coeliacs, the positive predictive value of EMA was 90.6%, IgA AGA 74.3% and IgG AGA 44.6%. In conclusion, EMA screening is an excellent test for the diagnosis and follow-up of CD, and for identification of its silent and latent forms. Antiendomysium antibodies, coeliac disease     

Human tissue transglutaminase enzyme linked immunosorbent assay outperforms both the guinea pig based tissue transglutaminase assay and anti-endomysium antibodies when screening for coeliac disease

Anti-endomysium antibodies (EMA) and antigliadin antibodies (AGA) are widely used when screening for coeliac disease (CD), although their specificity and sensitivity are suboptimal. The guinea pig tissue transglutaminase (tTG) assay also did not prove to be superior. A newly developed enzyme linked immunosorbent assay (Celikey), based on human tTG, might however have a better performance. We therefore investigated the sensitivity and specificity of this human IgA tTG assay in 101 patients with aspecific gastrointestinal complaints and compared this to guinea pig IgA tTG, AGA and EMA. A total of 52 patients with CD were investigated and 49 patients without CD. All had a small bowel biopsy. Our results showed that human IgA tTG had a sensitivity of 96% and a specificity of 100%. Guinea pig IgA-tTG had a sensitivity of 96% and a specificity of 92%. EMA had a sensitivity of 92% and a specificity of 90%. Both IgA AGA and IgG AGA had a sensitivity of 83% whilst having a specificity of 86% and 80% respectively. CONCLUSION: both the human IgA tissue transglutaminase enzyme linked immunosorbent assay and the guinea pig IgA tissue transglutaminase assay could better identify patients with coeliac disease than IgA anti-endomysium antibodies. Although in a larger series of control patients the specificity for the human IgA tissue transglutaminase enzyme linked immunosorbent assay might fall below 100%, in our opinion this is currently the serological method of choice in identifying patients with coeliac disease in the absence of IgA deficiency.     

Tissue transglutaminase autoantibodies and human leucocyte antigen in Down's syndrome patients with coeliac disease

The association between autoantibodies against tissue transglutaminase (tTG) and human leucocyte antigen (HLA)-DQB1 alleles was tested in Down's syndrome (DS) patients with and without coeliac disease (CD). Immunoglobulin A (IgA) and G (IgG) anti-tTG were measured in radioligand binding assays and compared with conventionally analysed IgA antibodies against gliadin (AGA) and IgA autoantibodies against endomysium (EMA) in 48 DS patients. HLA-DQB1 typing was carried out by polymerase chain reaction and hybridization with allele-specific probes in 41/48 patients. Both IgA-tTG and IgG-tTG, as well as EMA, were detected in 7/48 and AGA in 15/48 patients. Intestinal biopsy showed histopathological changes consistent with CD in 9/16 patients. HLA-DQB1 typing, available for 8/9 patients with and for 33/39 without CD, demonstrated that 5/8 with CD had DQB1*02 compared with 7/33 of those without ( p = 0.0345). In patients with anti-tTG, 5/6 had the DQB1*02 allele compared with 7/35 of those without ( p = 0.0053).

Conclusions: Anti-tTG are HLA-DQB1*02-associated autoantibodies which together could be useful screening tests for silent CD in DS patients. In patients with gastrointestinal symptoms or clinical signs of malabsorption, anti-tTG should be combined with AGA to detect other forms of enteropathies and CD.     

Celiac disease diagnosis in misdiagnosed children

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio <3:1 as index of intestinal atrophy. It is noticeable that a selective IgA deficiency was present in only 9 of 18 EMA IgG1 positive children. In addition, clinical symptoms, EMA IgG1, and mucosal atrophy disappeared after 8-10 mo on a gluten-free diet. Neither EMA IgA nor EMA IgG1 were detected in the children in the control groups. The other 12 children in study group showed no histologic abnormalities and were EMA IgG1 negative. In this study, we reveal a group of EMA IgG1 CD children without IgA deficiency. The diagnosis was based on the presence of gluten-dependent typical serological and histologic features of CD. Our data suggest that EMA IgG1 determination could be a new tool in the diagnostic workup of CD, useful in avoiding possible misdiagnosis.     

Prediction of silent celiac disease at diagnosis of childhood type 1 diabetes by tissue transglutaminase autoantibodies and HLA

Abstract: Aims: The aims were to estimate the diagnostic sensitivity and specificity of autoantibodies to tissue transglutaminase (IgA‐ and IgG‐tTG), gliadin (AGA) and endomysium (EMA) in relation to human leukocyte antigen (HLA)‐DQB1 alleles to identify silent celiac disease at diagnosis of type 1 diabetes. Methods: IgA‐ and IgG‐tTG were measured in radioligand binding assays in 165 type 1 diabetic patients. Data on HLA‐DQB1 were available for 148 patients and on both AGA and EMA for 164 patients. For patients considered positive for AGA or EMA, or both, an intestinal biopsy was suggested. HLA‐DQB1 typing was carried out by polymerase chain reaction and hybridization with allele specific probes. Results: Three patients, left out from further study of antibodies, but not from HLA‐DQB1 analysis, had treated celiac disease at diagnosis. Out of the other 162 type 1 diabetic patients tested, nine had IgA‐tTG, six IgG‐tTG, eight EMA, and 11 AGA. Biopsy was suggested for nine patients, of whom six showed villous atrophy, one did not and two refused to participate. Thus, silent celiac disease was probable in 8/162 and biopsy‐verified in 6/162, where five patients were AGA‐positive and six either EMA‐, IgA‐tTG‐ or IgG‐tTG‐positive. Of the 11 patients with celiac disease (three with treated and eight with silent celiac disease), 10 were HLA‐DQB1‐typed, of whom 65% (13/20) had the DQB1*02 allele, compared with 36% (100/276; p = 0.011) of those without celiac disease. IgA‐tTG levels were higher in patients having either *02 or *0302 (0.6; ?1.3–112.4 RU) compared with those not having these alleles (0.4; ?0.7–3.4 RU; p = 0.023). Conclusion: IgA‐tTG are HLA‐DQB1*02‐associated autoantibodies with high sensitivity and specificity for silent celiac disease at diagnosis of type 1 diabetes.     

A comparison between antigliadin antibodies and blood xylose in celiac disease]

We have compared serum antigliadin antibodies (AGA) with xylose absorption test in diagnosis and follow-up of pediatric celiac disease. Three groups of children were investigated: celiacs, affected by other gastrointestinal disease, healthy controls. On gluten diet AGA IgA, IgG and xylose test were abnormal in all celiac children. After only three months of gluten-free diet, abnormal AGA IgA values were found in 3%, AGA IgG in 63%, xylose test in 28% of children. Normal values for AGA IgA and IgG and for xylose test were found between 7 and 20 months. On challenge, after 1-4 months of gluten diet, abnormal AGA IgA and IgG values were found in 90% of cases, xylose test only in 27%. As far as the children with other gastrointestinal disease are concerned, 2% had abnormal values for AGA IgA, 22% for AGA IgG and 42% for xylose test. All healthy children had normal AGA IgA, IgG values and xylose test. Our date show AGA IgA the most specific laboratory test, among these investigated, for diagnosis and follow-up of celiac disease.     

Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies

The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61 children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in 6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD (3.5%). In three AGA- and EMA-positive subjects, permission for intestinal biopsy was refused, while in two AGA-positive and EMA-negative children, the intestinal mucosa was normal. Our study confirms the association of CD and DS, and suggests the usefulness of EMA determination as a test for selecting DS patients for intestinal biopsy.     

Antibody reactivity against human and guinea pig tissue transglutaminase in children with celiac disease

BACKGROUND: Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions. The purposes of this study were to evaluate the clinical potential of circulating anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A antibodies in the diagnosis of childhood celiac disease and to investigate the extent of autoreactivity of these antibodies. METHODS: Included in this retrospective study were samples from 22 children with biopsy-verified celiac disease, 23 control subjects with disease, and 22 healthy control subjects without any known gastrointestinal or inflammatory disorders. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IgA antibodies specific for human and guinea pig tTGs. All samples were also analyzed for antibodies to gliadin and endomysium (EMA). RESULTS: The concentrations of IgA specific for human and guinea pig tTGs correlated with the small intestinal villous structure and the serum levels of IgA EMA. The tTG ELISAs exhibited a high specificity and sensitivity for detection of untreated celiac disease. The human erythrocyte IgA tTG ELISA had the highest sensitivity (100%) and a specificity of 98%. The IgA EMA method had a sensitivity of 95% and the highest specificity (100%) of all tests. CONCLUSIONS: Our results provide additional support to the concept that anti-tTG IgA antibodies can be used as a highly discriminatory serologic marker for celiac disease and that measurements of these autoreactive antibodies may in the future be used as an alternative to the EMA test.     

Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease

Serum and salivary IgA and IgG antigliadin antibodies were determined by an enzyme-linked immunosorbent assay in 18 children with villous atrophy and 30 children on a gluten-free diet for coeliac disease in whom normal intestinal mucosa was found. Serum IgA anti-endomysium antibodies were also determined by an immunofluorescence method in these children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the highest sensitivity (100 and 94.4%, respectively), followed by serum IgA antibodies to gliadin (72.2%), salivary IgA antigliadin (61.2%) and IgG antigliadin (50%) antibodies. The highest specificity was found for serum IgA anti-endomysium (100%) and IgA antigliadin (96.6%) antibodies and salivary IgA and IgG antigliadin antibodies (93.3%), while serum IgG antigliadin antibodies were found to be least specific (63.3%)     

Antigliadin and antiendomysium antibody determination for coeliac disease.

The value of IgG and IgA gliadin antibodies (AGA) was compared with that of IgA endomysium antibodies (EMA) for the diagnosis of coeliac disease. Three hundred and six of 340 (90%) children with untreated coeliac disease (flat mucosa) had EMA and 338/340 (99.4%) had IgG AGA and/or IgA AGA. Only 1/340 (a 7 year old boy with selective IgA deficiency) had neither AGA nor EMA. Absence of EMA is more frequent in coeliac patients younger than 2 years than in older patients (32/277 compared with 1/62). EMA were present in 4/211 (2%) of comparison subjects (normal mucosa), IgA AGA in 12/211 (6%), and IgG AGA in 74/211 (35%). The specificity of AGA cannot be calculated from these figures as they are biased. The combined determination of AGA and EMA, taking advantage of the high sensitivity of AGA and the high specificity of EMA, gives an excellent prediction of the condition of the mucosa: 247/248 patients (99.6%) with positive EMA and positive IgG AGA and IgA AGA had a flat mucosa, whereas 136/137 patients (99.3%) with neither AGA nor EMA had a normal mucosa. During a gluten free diet EMA and AGA disappear. Their presence or absence is therefore an indicator of dietary compliance. After reintroduction of gluten into the diet 110/134 (82%) of the patients who had a flat mucosa at diagnosis relapsed, but 24/134 still had a normal mucosa after 2-15 years of challenge. All these patients without a morphological relapse were less than 2 years old at diagnosis so we conclude that patients who are young at diagnosis should be challenged. AGA often reappear earlier than EMA. After one month of challenge 93% of patients are AGA and 69% EMA positive. After more than three years of gluten intake the percentage of AGA positive patients decreased to about 50% whereas the percentage of EMA positive sera was then highest (93%). Therefore EMA are more sensitive for the detection of 'silent' relapse after prolonged periods of gluten intake.     

Serum antibodies to dietary antigens: a prospective study of the diagnostic usefulness in celiac disease of children

We examined 1,541 consecutive serum samples from 707 children with suspected food intolerance and 32 with treated celiac disease (CD) for IgG and IgA antibody reactivities to antigens from gluten, egg, and cow's milk by an enzyme-linked immunosorbent assay (ELISA). Samples from 72 patients showed increased IgA and/or IgG reactivity to gluten antigens; four were known CD patients not complying with a gluten-free diet, 13 were suspected CD patients challenged with gluten, and 30 most likely had CD as suggested by small intestinal villous atrophy and histological and/or clinical improvement on a gluten-free diet. The remainder with increased antigluten activity had other disorders that might have affected mucosal permeability. Nevertheless, the median IgA reactivity to gluten was significantly higher in the CD group, and the probability for CD increased from 25 to 100% when this reactivity was above 2.4 optical density (OD) units in our ELISA. Sixteen CD patients (but none of those without CD) had IgA reactivity to gluten higher than 2.4 OD units. We conclude that ELISA determinations of levels of serum antibodies reacting to dietary antigens is a valuable adjunct in the diagnosis of CD in children.     

Antigliadin and antireticulin antibodies in children with dermatitis herpetiformis

The serum samples of 27 children with dermatitis herpetiformis (DH) were examined for the presence of antigliadin (AGA) and antireticulin (ARA) antibodies. AGA were determined with an enzyme-linked immunosorbent assay (ELISA) and ARA with an immunofluorescence method. Increased IgA or IgG class AGA levels were found in four of ten children on a normal diet, in two of 25 on a gluten-free diet (GFD), and in two of four children on gluten challenge. The corresponding figures for ARA were nine of ten, two of 25, and four of four, respectively. All nine patients with ARA on a normal diet had either subtotal or partial villous atrophy, whereas the patient negative for ARA had a normal jejunal mucosa. ARA were mostly of IgA class, and after gluten withdrawal, increased levels fell to normal range. Four children were challenged with gluten, and they all developed subtotal villous atrophy and demonstrated IgA class ARA. These results suggest that in childhood DH, ARA is a more sensitive indicator of gluten-sensitive enteropathy than AGA, but both antibody determinations can be used in monitoring adherence to GFD treatment.     

Antibodies to gliadin in children with coeliac disease.

We have measured antibodies to gliadin (AGA), bovine beta-lactoglobulin, and chicken egg ovalbumin with a four-layer solid phase radioimmunoassay (RIA) in 62 children and adolescents with coeliac disease and in 36 healthy controls. The geometric mean titre of IgG AGA in patients at initial diagnosis was more than 100-fold that of controls (p less than 0.0001). Even patients on gluten-free diet had significantly higher IgG AGA titres than the controls (p = 0.0001), the difference being more than 5-fold. All the 42 patients with active disease (30 at initial diagnosis and 12 after gluten challenge) had their IgG AGA titre above 1,000, as compared with 2 (5.7%) of the 35 controls (p less than 0.0001). Both IgG and IgA AGA were quite sensitive and specific in identifying children with coeliac disease; the sensitivities for IgG and IgA AGA were 100% and 95.2%, the specificities 94.3% and 97.2%, respectively. We conclude that determination of IgG and IgA AGA with RIA is suitable for monitoring dietary compliance in children with coeliac disease, and the method is sensitive and specific for screening for coeliac disease in children.     

Antibodies to Gliadin in Children with Coeliac Disease

ABSTRACT. We have measured antibodies to gliadin (AGA), bovine β-lactoglobulin, and chicken egg ovalbumin with a four-layer solid phase radioimmunoassay (RIA) in 62 children and adolescents with coeliac disease and in 36 healthy controls. The geometric mean titre of IgG AGA in patients at initial diagnosis was more than 100-fold that of controls ( p <0.0001). Even patients on gluten-free diet had significantly higher IgG AGA titres than the controls ( p = 0.0001), the difference being more than 5-fold. All the 42 patients with active disease (30 at initial diagnosis and 12 after gluten challenge) had their IgG AGA titre above 1000, as compared with 2 (5.7%) of the 35 controls ( p <0.0001). Both IgG and IgA AGA were quite sensitive and specific in identifying children with coeliac disease; the sensitivities for IgG and IgA AGA were 100% and 95.2%, the specificities 94.3% and 97.2%, respectively. We conclude that determination of IgG and IgA AGA with RIA is suitable for monitoring dietary compliance in children with coeliac disease, and the method is sensitive and specific for screening for coeliac disease in children.     

Antibodies to gliadin, endomysium, and tissue transglutaminase for the diagnosis of celiac disease.

BACKGROUND: Tissue transglutaminase has recently been identified as the main autoantigen recognized by antiendomysial antibodies in celiac disease. Serum immunoglobulin (Ig)A antibodies to tissue transglutaminase (tTG-ab) determined by an enzyme-linked immunosorbent assay (ELISA) technique have been reported to correlate closely with IgA antiendomysial antibodies (EMA). The purpose of this study was to assess the sensitivity, specificity, and predictive value of tTG-ab measured by a commercially available ELISA technique, compared with those of EMA and IgA antigliadin antibodies (AGA) for the diagnosis of celiac disease. METHODS: Twenty-seven serum samples were obtained from patients with untreated celiac disease, 37 from patients who had had gluten withdrawn from their diets for varying time spans, and 34 from control subjects without celiac disease. All were younger than 14 years. Presence of tTG-ab and AGA was determined by ELISA and of EMA by indirect immunofluorescence. RESULTS: Twenty-six of 27 serum samples obtained from patients at the time of diagnosis of celiac disease were AGA positive. All 27 (concordance rate 100%) were positive for EMA and tTG-ab. Of the 34 control subjects, 1 was for AGA and 2 for tTG-ab. All 34 were negative for EMA. Sensitivity, specificity, positive predictive value, and negative predictive value within this group were, for tTG-ab: 100%, 94%, 93%, and 100%, respectively; for EMA: all four indexes were 100%; and for AGA: 96%, 97%, 96%, and 97%, respectively. Of the 37 with treated celiac disease, 2 were AGA positive, 9 were EMA positive, and 6 were tTG-ab positive. The concordance rate between EMA and tTG-ab was 100% in the group with untreated celiac disease, 94% in the control subjects, and 76% in the group with treated celiac disease. CONCLUSIONS: Immunoglobulin A antibodies to tissue transglutaminase are new, highly sensitive, and specific markers of celiac disease. They can be determined easily by an accurate, comparatively cheap technique and thereby may advantageously replace the EMA marker traditionally used.     

Serum IgA and IgG gliadin antibodies and small intestinal mucosal damage in children

Serum immunoglobulin (Ig) A and IgG gliadin antibodies were determined with a simple, rapid, and inexpensive method--diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA)--and the results were related to small intestinal mucosal morphology in 234 children suspected of having malabsorption. Fifty-six of 58 children with flat intestinal mucosa had increased IgA and/or IgG gliadin antibody levels (sensitivity 97%). Fifty-four of the 58 children had celiac disease (CD) (n = 25) or probable CD (n = 29). Four children with flat mucosa had cow's milk protein and/or soy protein intolerance and three of these had increased gliadin antibody levels. Seventeen percent of 132 children with normal intestinal mucosa had increased IgA and/or IgG gliadin antibody levels. IgA and IgG gliadin antibody levels decreased significantly in the celiac children on a gluten-free diet and increased significantly after gluten challenge. Determination of serum IgA and IgG gliadin antibodies by means of DIG-ELISA is a sensitive test for small intestinal mucosal damage in children. When malabsorption is suspected, we suggest that this assay be used to select children for a small intestinal biopsy. It is also very useful for the follow-up of adherence to a gluten-free diet and to determine the effect of gluten challenge in celiac children.     

High prevalence of coeliac disease in Danish children with type I diabetes mellitus

The purpose of this population-based study was to determine the prevalence of coeliac disease (CD) in 106 Danish children (age 2-18 y) with type I diabetes mellitus compared with 106 ageand sex-matched healthy controls. Serum samples were analysed for immunoglobulin A (IgA) and IgG gliadin antibodies by enzyme-linked immunosorbent assay (ELISA), for IgA endomysium antibodies (EMA) by immunofluorescence and for IgA tissue transglutaminase antibodies (tTGA) by ELISA. None of the controls had EMA or tTGA. Two diabetics previously diagnosed with CD were antibody negative on a gluten-free diet. Ten diabetics had both EMA and tTGA. Intestinal biopsy was performed in nine of them. All biopsies showed a histological picture of partial or total villous atrophy confirming the diagnosis of CD. Diabetics with CD were significantly younger ( p = 0.026), had an earlier onset of diabetes ( p = 0.005), had a lower height standard deviation score ( p = 0.019) and more often had thyroid antibodies ( p = 0.040) compared with diabetics without CD.

Conclusion: A high prevalence of CD of 10.4% (95% confidence interval 4.6-16.2%) was found in young Danish diabetics. Early onset of diabetes may predispose to CD. Routine serological screening for CD may be valuable in patients with type I diabetes mellitus.     

The prevalence of celiac disease in at-risk groups of children in the United States

OBJECTIVE: In contrast to its prevalence in Europe, celiac disease (CD) is considered rare in the United States. We aimed to determine the prevalence of CD in children presenting with symptoms or conditions associated with CD. STUDY DESIGN: Individuals aged 6 months to 20 years were screened for IgG and IgA antigliadin (AGA-IgG and AGA-IgA) and antiendomysium (EMA) antibodies. Those with only elevated AGA-IgG were screened for selective IgA deficiency. Patients with elevated EMA, or AGA-IgG elevation and selective IgA deficiency, were advised to undergo small intestinal biopsy. RESULTS: A total of 1200 individuals were studied; 34 were EMA positive-26 (19 EMA positive) consented to biopsy and 21 had CD, giving a prevalence of 1 in 57 (21/1200). Including the 15 EMA positive patients who refused a biopsy, the prevalence of CD in this study could be as high as 1 in 33 (36/1200). CONCLUSIONS: CD is not rare in the United States and may be as common as in Europe. AGA and EMA are useful for identifying patients who should undergo a small intestinal biopsy.     

Tissue transglutaminase immunoglobulin isotypes in children with untreated and treated celiac disease

OBJECTIVES: Tissue transglutaminase (tTG) autoantibodies are serologic markers for celiac disease (CD). The aim was to determine the diagnostic sensitivity and specificity of different immunoglobulin isotypes against tTG. METHODS: Immunoglobulin A (IgA)-tTG, IgG-tTG, and IgG1-tTG were measured in radioligand binding assays in 67 children with untreated and 89 children with treated CD and compared with 48 biopsy controls. IgM-tTG was measured in children with untreated CD and in biopsy controls. IgA endomysial autoantibodies (EMA) were analyzed in all children using an immunofluorescence method. RESULTS: The sensitivity of IgA-tTG and IgG-tTG was 85.1% (57 of 67) and 83.6% (56 of 67), respectively, which both increased to 93.8% (45 of 48) in children diagnosed at age 2 years or older. Both had a specificity of 93.8% (45 of 48). IgA-EMA had a sensitivity of 80.6% (54 of 67) and a specificity of 91.7% (44 of 48). In treated CD, IgA-tTG and IgG-tTG were detected in 21.3% (19 of 89) and in 14.6% (13 of 89), respectively, despite negative EMA titers. IgG1-tTG was correlated to age (r = -0.47, P = 0.0005) and detected in 50.7% (34 of 67) with untreated CD compared with 11.2% (10 of 89) with treated CD and with 4.2% (2 of 48) of biopsy controls ( P < 0.0001, respectively). IgM-tTG was detected in 1.5% (1 of 67) with untreated CD and in none of biopsy controls. CONCLUSION: IgA-tTG and IgG-tTG analyzed in radioligand binding assays are equivalent to IgA-EMA as screening tests for CD during childhood, but an intestinal biopsy is still the method of choice to establish the diagnosis. Although IgG1-tTG was more common at young age of diagnosis, both IgG1-tTG and IgM-tTG had low specificity and sensitivity and may not be useful as screening tests for CD.