J. Kerckhaert

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice

OBJECTIVE:We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives.METHODS:The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2–76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy).RESULTS:The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA.CONCLUSIONS:Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.

BACKGROUND/OBJECTIVE Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. MATERIALS AND METHODS Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. RESULTS Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. CONCLUSION A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.

SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality

UNLABELLED The aim of this study was to assess the correlation of sugar absorption test (SAT) using Lactulose/Mannitol/Sucrose (LMS), with IgA-endomysium (EMA), and IgA-gliadin (AGA) antibodies in relation to the severity of the intestinal mucosal damage in adult coeliacs. We have differentiated the Marsh classification in partial villous atrophy (VA) (III a), subtotal VA (III b), and total VA (III c). Twenty-nine untreated adults coeliacs, with a mean age of 47 years, range 20-76 yrs were studied over 3 years. SAT, IgA-AGA and IgA EMA were performed in 29 consecutive coeliac patients with villous atrophy on a gluten containing diets. RESULTS Histopathological evaluation of small intestinal mucosa showed a partial VA in 14/29, subtotal VA in 10/29 and total VA in 5/29. All coeliacs with total VA had positive EMA (5/5 100%). However in coeliacs with partial VA sensitivity of EMA was poor (4/14 29%). Sensitivity of EMA in patients with subtotal VA was 50% (5/10). AGA was raised in 3/14 (21%), 6/10 (60%), and in 4/5 (80%) coeliacs with partial, subtotal and total VA respectively. AGA was raised in 13/29 (sensitivity 45%). SAT was abnormal in 26/29 (sensitivity: 89%). One patient had abnormal SAT, EMA and AGA. Eleven of 29 patients (38%) were negative for AGA and EMA, but SAT was abnormal in 10 of them. One patient was positive for EMA, negative for AGA, normal for SAT. EMA and/or AGA were positive in 18/29 (sensitivity 62%). Our study suggests that negative predictive value of serology should be interpreted cautiously since coeliacs with partial VA are negative in serology. Over the last ten years SAT and EMA have been accepted as screening tools for CD. SAT seems to be more sensitive than serology. However there is no standardized agreement in the literature for serology and SAT. A combination of SAT and serology may provide a good sensitivity in order to detect that subgroup of coeliacs with milder histopathological abnormality.

Anti-endomysium test remains unreliable in celiacs with milder villous atrophy in spite of use of different substrates. A comparative evaluation of human umbilical cord and monkey ileum for the serological diagnosis of celiac disease

It is well established that circulating antibodies offer the prospect of a noninvasive diagnostic screening test in coeliac patients with severe histopathological abnormalities. Human umbilical cord as a substitute for monkey esophagus might be an improvement in screening for celiac disease (CD). METHODS: Serum from 260 adults and children > 2 yrs including 49 follow-up celiacs and 211 suspected for CD referred to our laboratory were screened for IgA, antiendomysium (EMA) using monkey ileum (MI) and Human Umbilical Cord (HUC). The prevalence of EMA detected on MI with that on HUC were compared. Fifty-seven of 211 suspected celiacs underwent a small intestinal biopsy. RESULTS: Twenty-four out of 57 had CD and EMA test was positive in 18124 using both MI and HUC (sensitivity 75%). Partial villous atrophy was seen in all 6 EMA negative patients and total/subtotal villous atrophy was demonstrated in 18124 cases with positive EMA. Both substrates detected identical positive cases and neither gave falls-positive results. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on ML One patient was EMA negative on MI but positive on HUC and one patient with EMA positive on MI had EMA negative on HUC. Only four of 49 celiacs on gluten free diet with persisted total villous atrophy had positive EMA. Seven EMA positives of study group will undergo a small intestinal biopsy in near future. The rest of consecutive cases had a negative EMA on both HUC and MI (specificity 100%). CONCLUSION: EMA sensitivity on MI is similar to that found on HUC. Furthermore HUC offer an easily available antigen with reduce costs which could avoid the use of endangered species. A positive result for antiendomysium in follow-up celiacs on gluten free diet indicates serious tissue damage and severe histopathological abnormalities in upper small intestine. However a negative result for EMA does not exclude the diagnosis of CD. All patients with minor villous atrophy were EMA negative using both substrates. This means that a positive EMA is seen mostly in those celiac with severe tissue damage (total/subtotal villous atrophy) in spite of using different substrates. Using HUC as a substrate for EMA may provide the same sensitivity and specificity as offered by the test using MI in both partial or total villous atrophy.