Dietary compliance in screening-detected coeliac disease adolescents

In 1992–94 we screened 6315 students for coeliac disease (CD) by testing antigliadin antibodies (AGA) as the first-level investigation. We found 28 biopsy-proven coeliac patients who were invited to start the gluten-free diet (GFD). The aim of this study was a clinical and laboratory follow-up in these screening–detected coeliac adolescents. Patients were 17 females and 11 males with a mean age at diagnosis of 12.8 ± 1 years (range 11–14). Mean follow-up duration time was 23 ± 7 months (range 9–37). Twenty-three of the 28 screening-detected coeliac patients came to the control visit, 3 refused the follow-up and 2 subjects were not found. Twelve patients (52.2%) stated that they never ate any gluten-containing food, while 11 of them (47.8%) reported occasional transgressions to the diet. GFD acceptance was reported as good ( n = 6), moderate ( n = 11) or low ( n = 6). After starting the GFD, signs of improvement were seen in most patients, such as weight gain, increased height velocity and increased feeling of well-being. AGA (both IgG and IgA classes) and antiendomysium antibodies (AEA) were normal in 19 subjects, 2 cases had IgG-AG A and AEA positivity, 1 patient showed abnormal AGA and AEA levels, while isolated IgA-AGA positivity persisted in 1 case. This study shows that even silent CD cases can clinically benefit from the GFD. The consequences of occasional transgressions to the GFD remain unclear.     

Prevalence of coeliac disease in diabetic children and adolescents

Screening for coeliac disease (CD) with serum antigliadin antibodies (AGA) was performed in 1032 diabetic children and adolescents. In 8 children CD had been diagnosed before study entry. Of the remaining 1024 children, 33 had an elevated AGA titre in the first serum sample. On follow-up an elevated AGA titre was confirmed in only 17 of 31 patients. Nine of the repeatedly positive patients underwent jejunal biopsy, and CD was diagnosed in two asymptomatic patients; both were positive for IgG- and IgA-AGA. Among 10 AGA-positive patients in whom biopsies could not be performed, only 1 showed IgA-AGA and thus carried a high risk for CD. From our results we estimate a prevalence of CD in Swiss and German diabetic children between 1.1% and 1.3%. Falsepositive AGA titres occurred significantly more often in patients with diabetes duration of less than 1 year. AGA testing teached a specificity of 99% if performed at least 1 year after the onset of diabetes. Children suffering from both diabetes and CD showed a diabetes manifestation at a significantly younger age than non-coeliac patients, whereas CD tended to be diagnosed at a remarkably late age.Abbreviations AGA antigliadin antibodies - CD coeliac disease - FIST fluorescent immunosorbent test - IDDM insulindependent diabetes mellitus     

Usefulness of antiendomysial antibodies as a serological marker in coeliac children

The new diagnostic criteria of coeliac disease (CD) give more importance to serological markers. Immunoglobulin A antiendomysial antibodies (IgA-EmA) were determined in 138 sera from 79 coeliac children and the antibody levels compared to IgG and IgA antigliadin antibodies (IgG-AGA, IgA-AGA) in the sera. The assessment was also carried out in 29 children with other gastrointestinal diseases, 29 with non-gastrointestinal diseases and 35 healthy children. The IgA-EmA had a 91.4% specificity and a 88.4% sensitivity for active CD. The corresponding figures were 89.8% and 64.4% for IgA-AGA and 73.7% and 86.2% for IgG-AGA, respectively. The results of IgA-EmA determinations were concordant with the intestinal biopsy findings in 90% of cases, versus 80% for IgA-AGA and 83% for IgG-AGA. In most of the discordant cases the biopsy showed only minor changes, making the classification difficult. All patients with positive IgA₂-EmA also had positive IgA₁ EmA antibodies. IgA-EmA are an excellent serological marker of CD activity in children and they are useful to decrease the number of intestinal biopsies which are needed to confirm the diagnosis in coeliac patients.     

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     

Value of antigliadin antibodies (AGA) in latent coeliac disease (CD)

BACKGROUND: The term latent coeliac disease (CD) is applied to patients who were previously shown to have a normal jejunal mucosa on a free diet. The aim of this study was to determine whether a high AGA value in the serum of patients with coeliac symptoms can also be regarded by itself, without typical mucosal atrophy, as a marker of latent CD, as some authors suggest in relatives of celiac patients. METHODS: We observed 31 patients with suspected CD and pathological values of serum IgA ang IgG AGA. In all we performed intestinal biopsy, assayed antiendomisium antibodies (AEA) in serum, AGA IgA, IgG, and IgM in duodenal jejunal fluid and in some of the lymphocytcs CD3+ gamma/delta+ in the lamina propria of the intestinal mucosa. RESULTS: In this study only pathological values of serum AGA without mucosa atrophy don't seem to be markers of latent CD, but an aspecific allergic response. CONCLUSIONS: As shown by other authors serum AEA, intestinal fluid AGA IgM and lamina propria lymphocytes CD3+ gamma/delta+ seem markers of latent CD.     

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.     

Prevalence of coeliac disease in diabetic children and their first-degree relatives in West Algeria: screening with serological markers

Atypical and relatively silent forms of coeliac disease (CD) have been described in insulin-dependent diabetes mellitus (IDDM). Our aim was to evaluate the prevalence of CD-IDDM with serological markers and to investigate the presence of CD in the IDDM first-degree relatives. During 1993 94 we explored 116 IDDM patients reported as new cases and 381 first-degree relatives of IDDM patients. Determination of IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) was made. Jejunal biopsy was performed in symptomatic patients or in those with positive serological markers, (i) Nineteen IDDM-CD were identified and 5 were suspected. Thus, the prevalence of CD in IDDM patients was between 16.4 and 20%. AGA and/or AEA were abnormal in 13 and normal in 5. Sensitivity was 80% for the three tests when used simultaneously and specificity was 100%. (ii) In the family study, 26 sera of asymptomatic first-degree relatives of IDDM patients were positive for at least one of the serological markers; 13 of them had villous atrophy. Systematic serological screening in IDDM allowed us to detect CD and evaluate the true incidence.     

Increased serum IL-2R levels in coeliac disease are related to CD4 but not CD8 antigens.

Forty-three coeliac children, ranging from 1 year and 3 months to 14 years and 9 months, were studied. Twenty-eight patients were in an active phase of the disease, and 15 were in remission. The criteria of coeliac disease (CD) activity were established according to the results of IgA anti-endomysial antibodies (IgA-AEm). Interleukin 2 receptor (IL-2R) and CD4 and CD8 antigens were measured in serum samples by an ELISA technique using two noncompetitive monoclonal antibodies. Antigliadin antibodies of IgG (IgG-AGA) and IgA (IgA-AGA) classes were also measured. The AEm-positive coeliac patient group showed values of 1,860 +/- 948 U/ml for IL-2R, 430 +/- 228 U/ml for CD8, and 36.8 +/- 25.1 U/ml for CD4. AEm-negative patients showed values of 980 +/- 436 U/ml, 350 +/- 243 U/ml, and 24.1 +/- 20 U/ml, respectively. IL-2R levels were the only ones significantly elevated (p < 0.005) in the active coeliac group. On the other hand, IgG-AGA and IgA-AGA were both clearly increased (p < 0.001). IL-2R levels in active coeliac patients correlated with CD4 levels (p < 0.05), but not with CD8, IgG-AGA, and IgA-AGA levels. We also found a surprising negative correlation between AEm antibodies of IgA2 class with both IL-2R (r = 0.471; p < 0.05) and CD8 (r = 0.616; p < 0.05). The results show that in CD there is a lymphocyte activation affecting mainly CD4+ cells and not correlated with serum AGA levels, suggesting an independence of both immunological phenomena and probably with different locations of origin.     

High prevalence of undiagnosed coeliae disease in 5280 Italian students screened by antigliadin antibodies

Many cases of coeliae disease are currently undiagnosed. We carried out a pilot study on screening for coeliae disease in a school population. The screening protocol consisted of three parts: (1) IgG and IgA antigliadin antibody (AGA) assay; (2) antiendomysium antibody and total serum IgA determinations; (3) jejunal biopsy. A total of 5280 students aged 11-15 years (71.7% of the eligible population) underwent the first evaluation; 113 subjects performed the second tests and 35 of these needed the third investigation. Coeliae disease was diagnosed in 23 cases, most of which were atypical or silent forms. The prevalence of undiagnosed coeliae disease was 4.36 per 1000 screened subjects (95% CI 2.58-6.14) and 5.03 per 1000 (95% CI 3.41-6.65) in the general population. The ratio of known to undiagnosed cases was 1 to 6.4. This high prevalence of undiagnosed coeliae disease raises a number of problems that require further evaluation.     

IgA endomysium antibodies – an early predictor for celiac disease in children without villous atrophy

Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD).
Methods: Children with suspected CD and positive EMA (≥1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n = 133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n = 39; 59% female, mean age at the first biopsy 7.3 years, range 1.4–16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n = 94; 56% female; mean age 7.6 years at the first biopsy, range 0.70–17).
Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2–7 years (median 4.5 years).
Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.     

Screening for coeliac disease in apparently healthy blood donors

As gliadin is a common food antigen for large people, we have developed an ELIS A for the detection of class-specific antigliadin antibodies (AGA), with which sera from a large population of apparently healthy blood donors was analysed. A very high prevalence (1/256) of positive AGA was found. However, the positive predictive value (+PV) was found to be very low, 20% for IgA-AGA and 0% for IgG-AGA alone. When screening large populations with no or few symptoms, it is desirable to have a high +PV to avoid unnecessary biopsies. IgA antiendomyisum antibodies (IgA-EM A) were evaluated both as a single test and in combination with IgA-AGA. When screening individuals for CD in a population with no or few symptoms the easy and cheap IgA-AGA assay should be used as a first test and the IgA-EMA to verify the diagnosis and avoid unnecessary biopsies.     

Evaluation of a screening test for detection of IgA antigliadin antibodies in coeliac disease

The reliability of antigliadin antibodies of IgA and IgG classes for the diagnosis and follow-up of coeliac disease was evaluated by ELISA tests. Forty coeliac patients, 41 patients with other gastrointestinal diseases and 50 healthy subjects were studied. IgA antigliadin antibodies were detected in all patients on unrestricted diet and in those on a challenge with a gluten-containing diet. A low incidence of positivities was found in patients on a gluten free-diet, while no positivity was found in controls or gastrointestinal patients. IgG determination, in contrast, showed poor specificity. Our data suggest that a positive IgA antigliadin test may be a reliable marker for the presence of active coeliac disease, which should be confirmed by intestinal biopsy; it is, moreover, a good marker for monitoring patients, since elevated values might suggest non-compliance with the diet.     

Mass screening for coeliac disease using antihuman transglutaminase antibody assay.

AIMS: To determine coeliac disease prevalence by an anti-transglutaminase antibody assay in a large paediatric population; to evaluate acceptance of the screening programme, dietary compliance, and long term health effects. METHODS: Cross-sectional survey of 3188 schoolchildren (aged 6-12) and prospective follow up of diagnosed cases. Main outcome measures were: prevalence of coeliac disease defined by intestinal biopsy or positivity to both human tissue transglutaminase and anti-endomysium antibodies in HLA DQ2-8 positive subjects; percentage of children whose families accepted screening; dietary compliance as defined by negativity for anti-transglutaminase antibodies; and presence of clinical or laboratory abnormalities at 24 month follow up. RESULTS: The families of 3188/3665 children gave their consent (87%). Thirty biopsy proven coeliacs were identified (prevalence 1:106). Three other children testing positive for both coeliac related autoantibodies and HLA DQ2-8 but refusing biopsy were considered as having coeliac disease (prevalence 1:96). Of 33 cases, 12 had coeliac related symptoms. The 30 biopsy proven coeliacs followed a gluten-free diet. Of 28 subjects completing 18-24 months follow up, 20 (71.4%) were negative for anti-transglutaminase antibodies, while eight were slightly positive; symptoms resolved in all 12 symptomatic children. CONCLUSIONS: Prevalence of coeliac disease is high in Italian schoolchildren. Two thirds of cases were asymptomatic. Acceptance of the programme was good, as was dietary compliance. Given the high prevalence and possible complications of untreated coeliac disease, the availability of a valid screening method, and evidence of willingness to comply with dietary treatment population mass screening deserves careful consideration.     

Salivary IgA antigliadin antibody as a marker for coeliac disease.

In recent years, serum antibodies to gliadin (AGA) have been reported to be useful markers of coeliac disease. IgA AGA have also been found in intestinal secretions and saliva in coeliac disease and may offer a convenient, non-invasive screening test. In order to test this hypothesis, salivary and serum AGA were measured in children with coeliac disease proved by biopsy and compared with several control groups. Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of screening for this disease before intestinal biopsy.     

Prevalence of coeliac disease in diabetic children and adolescents in Sweden

The aim of this study was to determine the minimum prevalence of coeliac disease in a group of 459 diabetic children and adolescents. Six patients were already known to have coeliac disease. A total of 436 patients with type 1 diabetes mellitus aged 2–21 years and with age at onset at 2 months to 17 years at three paediatric departments agreed to participate in the study. All patients were tested for gliadin IgA antibodies with a commercial kit (Pharmacia Gluten IgA EIA). Later, serum was tested for reticulin IgA/IgG antibodies. Nineteen patients had elevated gliadin IgA levels (>25 AU). Eighteen underwent jejunal biopsy. Ten had total or subtotal villous atrophy. These 10 patients were reticulin IgA-positive. Of 417 gliadin IgA-negative patients, 408 were reticulin IgA/IgG-negative. Of 6 reticulin IgA-positive patients, 3 had total or subtotal villous atrophy. All 3 had become gliadin IgA-positive at the time of biopsy. Among 3 reticulin IgG-positive patients with IgA deficiency, 2 had total villous atrophy: 1 was not willing to be biopsied. Patients with total or subtotal villous atrophy were judged as having coeliac disease and were recommended a gluten-free diet. Within 2 months, gliadin IgA levels were normal in patients adhering to the diet. Five patients have gone through a second jejunal biopsy to date with normal histology in all 5. The 15 newly diagnosed patients with coeliac disease plus 6 already known patients with coeliac disease and type 1 diabetes mellitus gave a minimum prevalence of coeliac disease in diabetic children and adolescents of 21/459 = 4.6%.     

Dental enamel defects and screening for coeliac disease

Specific dental enamel defects (DEDs) in permanent teeth are frequently observed in coeliac patients. We examined the permanent teeth in 6949 secondary school children living in Trieste (78% of 8724 children born between 1978 and 1982). Children with DEDs were tested for serum antigliadin antibodies (AGAs) and antiendomysium antibodies (AEAs), and those positive for serum AGAs and/or AEAs underwent intestinal biopsy. Specific DEDs were observed in 52 children (0.59% of the total population examined). Serum AGAs and/or AEAs were positive in 10 cases. Nine patients underwent intestinal biopsy (one refused) and in four cases a flat mucosa was documented (one with short stature, three completely asymptomatic). The known incidence of CD in the study area was 1:1000 before the study programme and 1:670 (an increase of 44%) after it. Dental enamel inspection may be utilized for detecting undiagnosed coeliac disease in symptom–free schoolchildren. This clinical test is probably less sensitive than serum AGA screening test, but deserves some consideration because it is cheap, easy to perform and well accepted by the population.     

High prevalence of coeliac disease in siblings of children with type 1 diabetes

Coeliac disease has been shown to occur more frequently among first-degree relatives of diabetic patients than in the general population. Our objective was to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in determining the genetic susceptibility to coeliac disease (CD) in these subjects. We investigated 240 siblings of diabetic children from 213 families (125 males and 115 females, aged 12.6±4.9 years, mean ± SD). All subjects were tested for the total IgA level to exclude IgA deficiency, and for endomysium IgA to disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead. Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA-DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in 9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six children, two had a normal mucosal finding and one refused the biopsy. The HLA-DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than in siblings without EMA (33%), corrected P =0.031. Conclusion:The 3.8% frequency of coeliac disease found in siblings of diabetic children is close to the 4.3% found previously in Czech children with type 1 diabetes mellitus and is substantially higher than the rate in the healthy children population.     

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.     

Increased prevalence of coeliac disease in diabetes.

A total of 215 diabetic children were screened for coeliac disease by determination of class specific serum reticulin antibody. Nine children were positive for reticulin antibody and all underwent biopsy of the small intestine. Four new cases of coeliac disease were found; all of these children had IgA reticulin antibody. Two of three other children with a low titre of IgA reticulin antibody had partial villous atrophy. It was concluded that IgA class reticulin antibody was a good marker of coeliac disease in diabetic children. The prevalence of coeliac disease in these children was 1:43 (including one previously diagnosed case) and we suggest that diabetic children be screened routinely for reticulin antibody.     

Celiac disease in India: are they true cases of celiac disease?

BACKGROUND: In a developing country, many conditions other then celiac disease (CD) can give rise to villous atrophy. We therefore assessed the role of immunoglobulin A (IgA)-antigliadin antibody (AGA) in addition to the ESPGHAN criteria in the diagnosis of CD in 104 Indian children. METHODS: Consecutive children with suspected CD were evaluated over 3 years with an intention to diagnose CD. Complete hemogram, d-xylose absorption test, endoscopic duodenal biopsy, and IgA-AGA titers were performed in all. CD was diagnosed on the basis of modified ESPGHAN criteria irrespective of IgA-AGA positivity (>5 U/mL), and those diagnosed were put on gluten-free diet and were monitored regularly. Children with suspected CD who had a normal duodenal biopsy result were taken as controls. RESULTS: The mean age of 50 children with CD was 6.3 +/- 2.6 years, with a male to female ratio of 3:2. The mean duration of symptoms was 3.4 +/- 2.2 years. Predominant symptoms were pallor in 96%, failure to thrive in 92%, and diarrhea in 80%. On follow-up (19.6 +/- 8 months), symptoms subsided within 16 +/- 9.8 days, and patients showed significant weight gain (mean weight at diagnoses and at last follow-up visit were 66% and 86% of expected, respectively; P < 0.001) and height gain (mean height at diagnoses and at last follow-up visit were 88% and 94% of expected, respectively; P = nonsignificant). The control group comprised 47 children with a mean age of 6.9 +/- 3 years. On comparing CD with controls, diarrhea, anemia, low weight, and stunting were significantly (P < 0.001) more frequent in patients with CD. Sensitivity and specificity of AGA at a cutoff value of 5 U/mL were 94% and 91.5% and at 10 U/mL 88% and 100%, respectively. Follow-up AGA test was performed in 42 of 47 positive cases. All showed significant decrease in AGA titer, and 29 (70%) had a negative test result. CONCLUSIONS: Indian children with CD are true cases of CD. They present late, diarrhea is absent in 20% of cases, and AGA test results show 88% of children without false-positive results at a cutoff value of 10 U/mL. However, AGA test with 94% sensitivity at a cutoff value of 5 U/mL can be used as screening test to select suspected cases for further workup.