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IgA Deficiency Causes False-Negative Endomysial Antibody Results in Celiac Disease

1996; Lippincott Williams & Wilkins; Volume: 23; Issue: 4 Linguagem: Inglês

10.1097/00005176-199611000-00029

1536-4801

Chris Rittmeyer, J. Marc Rhoads,

Microscopic Colitis

A number of papers have been published supporting the use of serological tests to diagnose celiac disease. IgA antiendomysial antibodies (IgA EmA) have generally been the most accurate. Sensitivities and specificities reported for detecting untreated celiac patients have been 89-100% and 97-100%, respectively (1-4). IgA antibodies to jejunum also hold promise as a highly accurate test for untreated celiac disease (5,6). A review of the literature revealed very few cases of untreated celiac disease missed by IgA EmA, and only two publications reported more than one individual case missed by IgA EmA (1-4,7-16). However, in the past year two consecutive pediatric cases of celiac disease were diagnosed at our medical center by clinical history, physical examination, small bowel biopsy, and subsequent dramatic clinical improvement on a gluten-free diet, yet both had false negative IgA EmA results. CASE REPORTS Patient 1 The patient was a 12-month-old girl admitted for evaluation of failure-to-thrive. She was reportedly healthy with normal development until ≈ 10 months of age when her parents noticed that she became pale, irritable, and less active. Her appetite and weight diminished dramatically. In the 2 months prior to admission, she lost 1.1 kg, dropping from the 25th to <5th percentile for weight. Complete blood count with differential, electrolytes, blood urea nitrogen, creatinine, and urinalysis were all within normal limits. Small bowel biopsy revealed crypt hyperplasia and villus atrophy consistent with celiac disease. IgA EmA and IgA AGA were negative and IgG AGA were positive (Table 1). The patient was placed on a gluten-free diet and exhibited dramatic improvement in appetite, activity, and growth. At 2 years of age she is at the 60th percentile for weight and height, and her development is normal. Patient 2 The patient was a 3½-year-old girl referred to our pediatric gastroenterology clinic for failure-to-thrive. She had poor appetite, vomiting, intermit-tent diarrhea, weight loss, and poor linear growth. She began to cross growth curve lines at ≈ 12 months of age. Four months prior to coming to our clinic, her thyroid-stimulating hormone was elevated, serum T4 was low, and albumin was 3.0. The patient was started on thyroid supplementation. After 4 months of thyroid supplementation her thyroid laboratory tests were normalized, but she had not grown, her albumin was 2.5, her appetite was worse, and she was very irritable. Family history indicated that her maternal grandmother died at age 72 and had had an autoimmune disease that included a goiter and thyroid insufficiency, hemolytic anemia, pernicious anemia, and possible mucocutaneous candidiasis. A maternal uncle also has mucocutaneous candidiasis. The patient's height and weight were at about the 5th percentile for a 2-year-old. We suspected celiac disease, and small bowel histology revealed crypt hyperplasia with villus atrophy. Her serum IgA EmA serology was negative (Table 1). Subsequently, the patient improved rapidly on a glutenfree diet. Four months later she had gained 3.3 kg and had grown 3.7 cm. IgA deficiency has been reported to be associated with celiac disease. Because we were surprised to find negative IgA EmA results in two consecutive patients with celiac disease when IgA EmA testing has been reported to be very sensitive for detecting celiac disease, we tested the serum IgA levels of our patients and found that both patients had IgA deficiency (Table 1). DISCUSSION Selective IgA deficiency is the most common immunodeficiency, occurring in 1:400 to 1:3,080 people (17,18). In these cases, IgA antibodies are abnormally low or totally absent, but IgG synthesis is normal. Many patients with selective IgA deficiency are healthy, but some have respiratory, autoimmune, atopic, oncologic, and/or GI illnesses (19,20). Celiac disease is 10 times more common in patients with IgA deficiency (21). Review of the literature revealed seven cases of IgA deficiency in celiac patients with false-negative IgA EmA results (4,22-24) and five cases of IgA deficiency with false-negative IgA antigliadin antibody results (24,25). Five other patients with active celiac disease and false-negative IgA EmA findings did not have IgA deficiency (9,10). The rate of IgA deficiency among patients with celiac disease has been reported to be 3% (26,27). Based on this rate, the chances of two consecutive celiac patients having IgA deficiency are <1:1,000. We suspect that the rate of IgA deficiency among celiac patients is higher than 3% and that IgA deficiency may account for a sizeable percentage of patients with active celiac disease who have false-negative IgA EmA and false-negative IgA antijejunal antibodies. All patients with active celiac disease and negative IgA EmA results should have serum IgA levels measured, and data should be compiled on the rate of IgA deficiency among celiac disease patients. Although all previous reports have found IgA EmA to be a very sensitive test, we have not found this to be the case because of IgA deficiency in our patients. In patients whose symptoms are likely to be from celiac disease, IgA EmA should not be measured in lieu of small bowel biopsy. If small bowel biopsy is consistent with celiac disease, then IgA EmA should be monitored. Initial IgA EmA positivity and subsequent disappearance of IgA EmA on a gluten-free diet should eliminate the need for repeat small bowel biopsy.