590
5. Teng NNH, Kaplan HS, Herbert HM, et al. Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci USA 1985; 82: 1790-94. 6. Spier SJ, Lavoie J-P, Cullor JS, Smith BP, Snyder JR, Sischo WM. Protection against clinical endotoxemia in horses by using plasma containing antibody to an Re mutant E coli (J5). Circ Shock 1989; 28: 235-48. 7. Calandra Tl, Glauser
MP, Schellekens J, Verhoef J. Treatment of gram-negative septic shock with human IgC antibody to Escherichia coli J5: a prospective, double-blind randomized trial. J Infect Dis 1988; 158: 312-19. 8. Sherry B, Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine and autocrine control of inflammatory responses. J Cell Biol 1988; 107: 1269-77. 9. Tracey KJ, Berther B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Nature 1986; 234: 470-74. 10. Exley AR, Cohen J, Buurman W, et al. Monoclonal antibody to TNF in severe septic shock. Lancet 1990; 335: 1275-77.
Diagnosis of coeliac disease Coeliac disease commonly defies diagnosis, and adults especially may present on numerous occasions before a small bowel biopsy provides confirmation. Early diagnosis is all the more important because treatment with a gluten-free diet seems to reduce the subsequent frequency of small intestinal malignant disease.’ A non-invasive test has long been sought with serological techniques. Antibodies to gluten, gliadin (AGA), reticulin (ARA), and endomysium (EMA) have been detected in 36-96% of untreated patients. However, sensitivities and specificities for AGA and ARA have varied widely from centre to centre. Performance of these methods can be improved by defming the classes of immunoglobulin involved,z but in clinical practice the results are often
disappointing. The two most recently discovered antibodiesEMA and human jejunal antibody (JAB)-may be useful for diagnosis and for monitoring the efficacy of treatment. Chorzelski et aP described an IgA class EMA in the sera of patients with dermatitis herpetifonnis and coeliac disease with greater sensitivity and specificity than AGA. These antibodies are directed at the lining of smooth muscle bundles of primates. Antibody titres correlate with the severity of the mucosal lesion; EMA and JAB disappear after gluten withdrawal and are specific for the jejunal mucosal atrophy of coeliac disease.44 Specificity and sensitivity of EMA are high-eg, in 5 one study in patients with subtotal villous atrophy,5 ARA was positive in 93% vs 100% for EMA. EMA was not detected in patients with other gastrointestinal diseases, and was found in only 1 of 100 blood donors, and this individual was later shown to have coeliac disease. Kapati and colleagues6 lately described JAB, a serum IgA antibody that binds to human jejunum in vitro. They found 93% of patients with untreated coeliac disease and 90% of those after gluten challenge had JAB vs none of those on a gluten-free diet. However, this antibody was not as helpful in younger children—only 71 % of those less than 2 years vs 95 % aged 2-18 years had JAB during gluten intake. Tissue
showed that JAB and AGA are different antibodies, whereas JAB and EMA are probably identical. The researchers propose that IgA JAB might be a target-organ-related autoantibody.
absorption studies
The clinical application of these antibodies awaits further assessment, but the potential value of serum antibody tests in raising the suspicion of coeliac disease was illustrated recently by Maki and colleagues.These workers reported 4 patients aged 1-32 years on a normal diet, who, when originally studied, were found to have normal jejunal mucosa, and at that time the ARA and EMA tests were also negative. When restudied 2-6-9 years later, the IgA ARA and EMA titres were significantly raised and small bowel biopsy specimens now showed villous atrophy. This study raises another new facet of coeliac disease, because until now most physicians would have accepted that a normal small bowel in a patient on a gluten-containing diet excludes coeliac disease for life. It is generally believed that the susceptibility to coeliac disease is inherited at birth. Thus a baby, on its first encounter with gluten, would manifest a jejunal atrophy, but the presentation and severity of symptoms might vary depending on how much bowel was involved. Development of coeliac disease in patients with a previously normally small bowel mucosa indicates either that they were not originally ingesting sufficient gluten to affect the villous architecture or that their sensitivity to gluten changed between the two biopsy specimens. Factors other than genetic susceptibility and gluten may then sometimes be required to induce mucosal damage in coeliac disease, as suggested by Kagnoff et al,8 who propose that coincident adenovirus infection may trigger the pathogenesis of the small bowel lesion. Our concepts of the condition and its diagnosis may therefore need to change, but meanwhile small bowel villous atrophy remains the only universally accepted confirmatory indicator of active coeliac disease. 1. Holmes GKT, Prior P, Lane MR, Pope D, Allan RN. Malignancy in coeliac disease—effect of a gluten free diet. Gut 1989; 30: 333-38. 2. Elewaut A, Dacremont G, Robberecht E, Leroy J, De-Baets MH. IgA isotyping of antigliadin antibodies: a possible clue for a less invasive diagnosis of coeliac disease. Clin Chim Acta 1989; 183:285-94. 3. Chorzelski TP, Beutner EA, Sulej J, et al. IgA anti-endomysium antibody: a new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol 1984; 111: 395-402. 4. Rossi TM, Kumar J, Lerner L, et al. Relationship of endomysial antibodies to jejunal mucosal pathology: specificity towards both symptomatic and asymptomatic celiacs. J Pediatr Gastroenterol Nutr 1988; 7: 858-63. 5. Hallstrom O. Comparison of IgA class reticulin and endomysium antibodies in coeliac disease and dermatitis herpetiformis. Gut 1989; 30: 1225-32. 6. Kápáti S, Bürgin-Wolff A, Krieg T, Meurer M, Stolz W, Braun-Falco O. Binding to human jejunum of serum IgA antibody from children with coeliac disease. Lancet 1990; 336: 1335-38. 7. Mäki M, Holan K, Koskimies S, Hallstrom O, Visakorpi JK. Normal small bowel biopsy followed by coeliac disease. Arch Dis Child 1990; 65: 1137-41. 8. Kagnoff MF, Paterson YJ, Kumar PJ, et al. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut 1987; 28: 995-1001.
5. Teng NNH, Kaplan HS, Herbert HM, et al. Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci USA 1985; 82: 1790-94. 6. Spier SJ, Lavoie J-P, Cullor JS, Smith BP, Snyder JR, Sischo WM. Protection against clinical endotoxemia in horses by using plasma containing antibody to an Re mutant E coli (J5). Circ Shock 1989; 28: 235-48. 7. Calandra Tl, Glauser
MP, Schellekens J, Verhoef J. Treatment of gram-negative septic shock with human IgC antibody to Escherichia coli J5: a prospective, double-blind randomized trial. J Infect Dis 1988; 158: 312-19. 8. Sherry B, Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine and autocrine control of inflammatory responses. J Cell Biol 1988; 107: 1269-77. 9. Tracey KJ, Berther B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Nature 1986; 234: 470-74. 10. Exley AR, Cohen J, Buurman W, et al. Monoclonal antibody to TNF in severe septic shock. Lancet 1990; 335: 1275-77.
Diagnosis of coeliac disease Coeliac disease commonly defies diagnosis, and adults especially may present on numerous occasions before a small bowel biopsy provides confirmation. Early diagnosis is all the more important because treatment with a gluten-free diet seems to reduce the subsequent frequency of small intestinal malignant disease.’ A non-invasive test has long been sought with serological techniques. Antibodies to gluten, gliadin (AGA), reticulin (ARA), and endomysium (EMA) have been detected in 36-96% of untreated patients. However, sensitivities and specificities for AGA and ARA have varied widely from centre to centre. Performance of these methods can be improved by defming the classes of immunoglobulin involved,z but in clinical practice the results are often
disappointing. The two most recently discovered antibodiesEMA and human jejunal antibody (JAB)-may be useful for diagnosis and for monitoring the efficacy of treatment. Chorzelski et aP described an IgA class EMA in the sera of patients with dermatitis herpetifonnis and coeliac disease with greater sensitivity and specificity than AGA. These antibodies are directed at the lining of smooth muscle bundles of primates. Antibody titres correlate with the severity of the mucosal lesion; EMA and JAB disappear after gluten withdrawal and are specific for the jejunal mucosal atrophy of coeliac disease.44 Specificity and sensitivity of EMA are high-eg, in 5 one study in patients with subtotal villous atrophy,5 ARA was positive in 93% vs 100% for EMA. EMA was not detected in patients with other gastrointestinal diseases, and was found in only 1 of 100 blood donors, and this individual was later shown to have coeliac disease. Kapati and colleagues6 lately described JAB, a serum IgA antibody that binds to human jejunum in vitro. They found 93% of patients with untreated coeliac disease and 90% of those after gluten challenge had JAB vs none of those on a gluten-free diet. However, this antibody was not as helpful in younger children—only 71 % of those less than 2 years vs 95 % aged 2-18 years had JAB during gluten intake. Tissue
showed that JAB and AGA are different antibodies, whereas JAB and EMA are probably identical. The researchers propose that IgA JAB might be a target-organ-related autoantibody.
absorption studies
The clinical application of these antibodies awaits further assessment, but the potential value of serum antibody tests in raising the suspicion of coeliac disease was illustrated recently by Maki and colleagues.These workers reported 4 patients aged 1-32 years on a normal diet, who, when originally studied, were found to have normal jejunal mucosa, and at that time the ARA and EMA tests were also negative. When restudied 2-6-9 years later, the IgA ARA and EMA titres were significantly raised and small bowel biopsy specimens now showed villous atrophy. This study raises another new facet of coeliac disease, because until now most physicians would have accepted that a normal small bowel in a patient on a gluten-containing diet excludes coeliac disease for life. It is generally believed that the susceptibility to coeliac disease is inherited at birth. Thus a baby, on its first encounter with gluten, would manifest a jejunal atrophy, but the presentation and severity of symptoms might vary depending on how much bowel was involved. Development of coeliac disease in patients with a previously normally small bowel mucosa indicates either that they were not originally ingesting sufficient gluten to affect the villous architecture or that their sensitivity to gluten changed between the two biopsy specimens. Factors other than genetic susceptibility and gluten may then sometimes be required to induce mucosal damage in coeliac disease, as suggested by Kagnoff et al,8 who propose that coincident adenovirus infection may trigger the pathogenesis of the small bowel lesion. Our concepts of the condition and its diagnosis may therefore need to change, but meanwhile small bowel villous atrophy remains the only universally accepted confirmatory indicator of active coeliac disease. 1. Holmes GKT, Prior P, Lane MR, Pope D, Allan RN. Malignancy in coeliac disease—effect of a gluten free diet. Gut 1989; 30: 333-38. 2. Elewaut A, Dacremont G, Robberecht E, Leroy J, De-Baets MH. IgA isotyping of antigliadin antibodies: a possible clue for a less invasive diagnosis of coeliac disease. Clin Chim Acta 1989; 183:285-94. 3. Chorzelski TP, Beutner EA, Sulej J, et al. IgA anti-endomysium antibody: a new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol 1984; 111: 395-402. 4. Rossi TM, Kumar J, Lerner L, et al. Relationship of endomysial antibodies to jejunal mucosal pathology: specificity towards both symptomatic and asymptomatic celiacs. J Pediatr Gastroenterol Nutr 1988; 7: 858-63. 5. Hallstrom O. Comparison of IgA class reticulin and endomysium antibodies in coeliac disease and dermatitis herpetiformis. Gut 1989; 30: 1225-32. 6. Kápáti S, Bürgin-Wolff A, Krieg T, Meurer M, Stolz W, Braun-Falco O. Binding to human jejunum of serum IgA antibody from children with coeliac disease. Lancet 1990; 336: 1335-38. 7. Mäki M, Holan K, Koskimies S, Hallstrom O, Visakorpi JK. Normal small bowel biopsy followed by coeliac disease. Arch Dis Child 1990; 65: 1137-41. 8. Kagnoff MF, Paterson YJ, Kumar PJ, et al. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut 1987; 28: 995-1001.
