Tissue transglutaminase as the autoantigen of coeliac disease

Abstract

Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or eYcacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis. (Gut 1997; 41: 561-564) Keywords: intestinal villous atrophy; ileum; secretory diarrhoea; bile acid malabsorption; microscopic colitis Villous atrophy of the terminal ileum is usually seen in patients with villous atrophy involving the whole length of the small bowel. The main aetiologies are coeliac disease and immunodeficiency syndromes, including HIV related immunodeficiency, common variable hypogammaglobulinaemia, and IgA deficiency. Ileal villous atrophy is seldom seen in the absence of duodenojejunal atrophy; its aetiologies are listed in Case reportsThe three patients (RM, DO, and ML) were women with severe chronic diarrhoea. Table 2 shows their main clinical characteristics. They were not taking any medication. The history of RM included the alternation of diarrhoea and constipation for 50 years, ovariectomy for benign ovarian neoplasm in 1938, tuberculous pleuritis in 1939, three episodes of intestinal obstruction due to adhesions, and hysterectomy in 1980 to treat an epidermoid carcinoma of the uterine cervix. The other two patients had no relevant history except for appendectomy. BIOLOGICAL AND MORPHOLOGICAL EXPLORATIONSCommon features of the three patients were the presence of high erythrocyte sedimentation rate of 35, 30, and 5-42 mm/h for RM, DO, and ML respectively, and a history of transient hypokalaemia (2-3.5 mEq/l). Table 2 presents results of ileal function tests. The results of the following laboratory investigations were in the normal range: haemoglobin; blood urea, glucose, uric acid, calcium, magnesium, iron, folates, and vitamin B 12 ; albumin, globulin fractions, plasma immunoglobulins, cholesterol, prothrombin time, D-xylose test; and stool analysis for pathogenic bacteria and parasites. Repeated searches for laxatives in the stools (phenolphthalein) and urine (anthraquinones) were negative. Faecal osmolarity was normal (280-320 mmol/l), and faecal electrolytes displayed an osmotic gap below 50 mmol/l. Levels of thyroid stimulating hormone (TSH), triiodothyronine, and thyroxine were in the normal range for RM and ML. DO had high TSH values (15.9 µg/ml (normal <4.5) and low triiodothyronine and thyroxine concentrations. Concentrations of serum vasoactive peptide, serotonin, and c...

Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease

“…In fact, this widely used ELISA is based on tTG which is a crude extract from guinea pig liver; it has been verified that Sigma tTG is composed of at least 14 different components23 and it is logical to hypothesise that in the sera of patients with chronic liver disease there could be antibodies for protein antigens from the liver matrix, probably common (or cross reacting) to humans and other mammals. In fact, in the second part of the study when we were able to test our sera for anti-tTG using a pure human recombinant tTG, we did not observe any false positive results: all 13 subjects with false positive anti-tTG values when evaluated with the ELISA based on tTG from guinea pig as antigen resulted in negative values with the new ELISA system.…”

Tissue Transglutaminase Autoantibodies in Patients with Non-Hodgkin’s Lymphoma

“…This hypothesis is also in agreement with the recent report of 49 patients with type 1 diabetes who were positive for anti-tTG antibodies, assayed by radiobinding assay with recombinant human t-TG, but negative for EmA [17]. Third, and in our opinion the most probable hypothesis, it is possible that the false positive anti-tTG results we observed depend on the nature of the antigen of the ELISA method we used; in fact, this test is based on tTG which is extracted from guinea pig liver and it must be remembered that Sigma tTG is composed of at least 14 different components [18]; thus, it is possible that in the sera of our patients there could be antibodies for protein antigens from the liver matrix, probably common to humans; in any case, it must be remembered that most of the gastroenterological studies published to date [2, 3, 4, 19]which reported a very high specificity of anti-tTG determination for CD diagnosis were performed with the same ELISA we used in the present study, based on tTG on guinea pig liver.…”

High Rate of Positive Anti-Tissue Transglutaminase Antibodies in Chronic Liver Disease

“…Recently, tissue transglutaminase (tTG) has been identified as the most important, if not the sole, antigen against which anti-endomysium antibodies are directed (1,2). tTG is a ubiquitous enzyme located in various cell types and implicated in cellular wound healing and apoptosis (3,4).…”