IgA endomysium antibody: a valuable tool in the screening of coeliac disease but not its follow-up.

The IgA antiendomysium antibody was found in 99 of 100 consecutive patients with adult untreated coeliac disease, whereas IgA and/or IgG antigliadin antibodies were found in 92 of the same patients. Twenty-nine of them, presenting with minimal, transient or apparently unrelated symptoms (subclinical presentation), were antiendomysium antibody positive, whereas antigliadin antibodies were present in 26. In 33 of them, we also investigated the relationship between circulating antiendomysium antibody and the persistence of jejunal lesions after the institution of a gluten-free diet. Although 24 treated coeliac patients turned out to be antiendomysium antibody negative, in 17 of them jejunal lesions persisted. The present study shows that IgA antiendomysium antibody is a highly sensitive and specific marker for both subclinical and classical coeliac disease, but that it is not a reliable test in the follow up of coeliac patients.

Subclinical celiac sprue. Increasing occurrence and clues to its diagnosis.

We have reviewed the clinical records of 226 consecutive adult patients with celiac sprue diagnosed in our department from 1972 to 1989. The study period has been divided into three subperiods of 6 years each (1972-1977, 1978-1983, 1984-1989). From the first to the third subperiod a significant increase in the number of new diagnoses and of the proportion of patients recognized by minor symptoms has been observed. These patients represent 50% of our series in the last 3 years of the study and 70% in 1989. Diagnosing subclinical forms of celiac sprue has significantly lowered the mean age at diagnosis and the female/male ratio. First-degree relatives of celiac patients; subjects who had a gluten-free diet for a period during childhood; patients with short stature, anemia, or amenorrhea of no obvious cause; or patients with unexplained immunological abnormalities are the groups in which most patients with subclinical celiac sprue have been found and in which potential patients should be sought. Helpful diagnostic tools include antigliadin antibody testing and the observation of absent or reduced Kerckring folds in the descending duodenum in the course of upper gastrointestinal endoscopy.

Gliadin immune reactivity is associated with overt and latent enteropathy in relatives of celiac patients.

Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.

Cytophilic antibodies cause leucocyte migration inhibition in coeliac disease.

Leucocyte migration inhibition in response to challenge with gluten fraction III was prevented by pretreatment of coeliac leucocytes with pronase, an enzyme that removes cytophilic antibodies. Leucocytes from healthy volunteers preincubated with serum from untreated and treated coeliac patients showed marked migration inhibition when incubated with gluten fraction III. No migration inhibition was observed with leucocytes from healthy volunteers preincubated with serum from patients with small bowel diseases other than coeliac disease and from other healthy volunteers. Untreated and treated coeliac patients who were leucocyte migration inhibition negative in the direct assay had migration indices in the sensitized range in the serum induced assay. This work is in keeping with a previous suggestion that in coeliac disease leucocyte migration inhibition induced by gluten fraction III is caused by cytophilic antibodies.

IgA antigliadin antibodies and persistence of jejunal lesions in adult coeliac disease.

In 46 adult patients with coeliac disease, 41 (89%) of whom were positive for IgA and/or IgG antigliadin antibodies (AGA) when untreated, we investigated after a gluten-free diet the relationship between the persistence of AGA, the persistence of jejunal lesions, and the duration and compliance with the diet. IgG AGA were positive in 21 coeliac patients (46%) after variable periods of gluten-free diet and were associated with IgA positivity only in 4 cases (9%). Both IgA and IgG AGA positivity appeared to be more related to the lack of improvement of the jejunal lesions than to the strictness and duration of gluten withdrawal. Nine coeliacs showed no improvement of jejunal lesions after the gluten-free diet. Of these 9, 4 showed persistent IgA AGA, while the remaining 5 resulted IgAAGA-negative as before when untreated. Though intestinal biopsy remains the best means of determining the positive effect of gluten withdrawal, the persistence of IgA AGA in treated coeliacs is always predictive of the persistence of severe jejunal lesions. The persistence of IgG AGA, on the contrary, should be regarded as an immunological memory.

Serological screening of coeliac disease: choosing the optimal procedure according to various prevalence values.

The aim of this study was to select the best approach for screening coeliac disease patients among populations with different grades of disease prevalence. The diagnostic performance was assessed of class A and G antigliadin antibodies and class A antiendomysium antibodies in 93 consecutive outpatients with suspected malabsorption, 44 of whom (47%) had coeliac disease according to duodenal histological tests. Class G antigliadin antibodies provided the worst diagnostic values, whereas a high diagnostic validity was found for the other two tests. The positive predictive value corrected for the disease prevalence expected in coeliac disease relatives (5%) and the general population (0.2%) fell to 30% and < 2% respectively for class A antigliadin antibodies, whereas it remained 100% for antiendomysium antibodies in both situations, providing an optimal value for their use as a screening test and as a valid alternative to duodenal biopsy when this is not feasible. The high cost of anti-endomysium antibodies and the invasive nature of duodenal biopsy prevent them being used widely as screening procedures. A cost effective two step approach was simulated measuring class A antigliadin antibodies in all subjects of the target population (first step), and performing a confirmation test (antiendomysium antibodies or duodenal biopsy) only in subjects positive for antigliadin antibodies. The results show that such a procedure should be recommended only for subjects with an expected low disease prevalence--that is, 5% for coeliac disease relatives and 0.2% for the general population--as the positive predictive value was always 100% with an acceptable false negative rate (6% and 11% respectively), irrespective of which of the two confirmation tests was used. This approach avoids the use of the confirmation test in 63% and 89% of subjects respectively for the two levels of prevalence, resulting in a considerable reduction of the cost. Patients seen for suspected malabsorption with an expected high prevalence of coeliac disease should not have such a serological screening procedure. In conclusion, antigliadin antibodies are useful to screen for asymptomatic coeliac disease in non-hospital communities if antiendomysium anti-bodies are used as a confirmation test: the latter is reasonable valid alternative to duodenal biopsy.

Subclinical coeliac disease is a frequent cause of iron-deficiency anaemia.

BACKGROUND: Although it is known that anaemia may be the only presenting symptom in coeliac disease, prevalence figures of unsuspected coeliac disease in anaemic patients are not available. The aim of this study was to assess the clinical usefulness of antigliadin and antiendomysial antibody tests in the diagnostic algorithm of anaemic patients. METHODS: Two hundred consecutive anaemic patients were tested for antigliadin antibodies, and those positive were also tested for antiendomysial antibodies. All patients positive for antigliadin and antiendomysial antibodies underwent intestinal biopsy. RESULTS: Sixteen patients were antigliadin antibody-positive, and 10 were also antiendomysial antibody-positive. In all 10 a jejunal biopsy was consistent with coeliac disease (prevalence, 5%). This prevalence rose to 8.5% when patients with macrocytic anaemia or with microcytic anaemia due to previous bleeding or responsive to oral iron therapy were excluded from the calculation. CONCLUSIONS: Coeliac disease is a frequent cause of iron-deficiency anaemia, and antigliadin and antiendomysial antibody tests should be always performed in the diagnostic algorithm of anaemic patients.

HLA-DP polymorphism in northern Italian celiac patients.

The contribution of HLA-DP genes to celiac disease susceptibility has been investigated in 95 Italian patients, 41 with childhood and 54 with adult disease onset. Polymerase chain reaction amplification, sequence-specific oligonucleotide probe hybridization and restriction fragment length polymorphism analyses have been carried out. All celiac patients and 56 out of 128 random healthy controls were DQw2-positive. The frequency of the DPB1*0101 allele was significantly increased (pc = 0.002, relative risk 5.21) in patients with celiac disease (23.2%) compared to the whole panel of controls (5.5%), but not to the 56 controls bearing DQw2 (10.7%). No significant difference in the frequency of DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult (22.2%) onset. The DPB1*0101 allele was associated with both the DR3-DQw2 and DR7-DQw2 haplotypes. Moreover, our study has not confirmed the association with DPB1*0402 and DPB1*0301 previously reported in celiac children from southern Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac disease susceptibility.

Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence.

Susceptibility to coeliac disease is strongly associated with some HLA class II antigens, encoded by the HLA-D region. Since the HLA-DQ locus seems to be primarily involved, we have analysed by polymerase chain reaction amplification and allele-specific oligonucleotide hybridization the most polymorphic region of the HLA-DQ A1 gene. No difference was observed between the 20 coeliac patients and 20 HLA-D-matched healthy controls who took part in the study. Furthermore, in patients and controls, the restriction fragment length polymorphism analysis of the HLA-DQ A gene using the restriction enzyme BglII did not disclose any specific disease-associated fragment. Our results are not consistent with a unique DQ A coeliac disease-associated sequence, but rather with the hypothesis that some polymorphic residues or allelic hypervariable regions, although found also in the normal population, can predispose to coeliac disease due to their higher frequency in this condition.