European Journal of Pediatrics

, Volume 139, Issue 2, pp 101–105

Small intestinal mucosa in coeliac disease and cow's milk protein intolerance: Morphometric and immunofluorescent studies

  • M. Stern
  • R. Dietrich
  • J. Müller
Original Investigations
  • 16 Downloads

Abstract

One hundred and twenty-five small intestinal biopsies from children with coeliac disease (CD), cow's milk protein intolerance (CMPI) and controls were compared by morphometric analysis, by counting intraepithelial lymphocytes (IEL) and by quantitative evaluation of immunoglobulin-containing cells of lamina propria. The double-stain immunofluorescent technique of Brandtzaeg and Baklien [2] was used, based on defined mucosal tissue units. A patchy enteropathy was found in 60% of CMPI, and in 14% of nonspecific changes, but never in CD. There was a significant difference in crypt depth between CD (360±80 μm) and CMPI (217±92 μm), even when lesions of equal grade were compared (P<0.015). IEL counts per 1000 epithelial cells showed even better discrimination between the groups (CD: 793±173, CMPI: 320±143, P<0.001). In CD, there was a relatively greater increase of IgM-cells (x4.9) and of IgG-cells (x4.2) than of IgA-cells (x2.6). Ig-cell changes outlasted the morphological lesion in CD on a gluten-free diet. In CMPI, IgM-cells (x2.3), IgG-cells (x2.5), and IgA-cells (x1.7) were proportionately increased, compared to controls. A special increase of IgE-cells in CMPI could not be substantiated.

By computerized stepwise discriminant analysis based upon crypt depth, villus/crypt-ratio, IEL-count, and counts of IgM-, IgG-, IgA-containing cells of lamina propria, accurate classification of patient groups was accomplished, even when only the initial biopsy data were analysed.

Key words

Coeliac disease Cow's milk protein intolerance Immunofluorescent technique Intraepithelial lymphocytes Morphometry 

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References

  1. 1.
    Bahna SL, Heiner DC (1980) Allergies to milk. Grune and Stratton, New YorkGoogle Scholar
  2. 2.
    Brandzaeg P, Baklien K (1976) Immunohistochemical studies of the formation and epithelial transport of immunoglobulins in normal and diseased human intestinal mucosa. Scand J Gastroenterol (Suppl 36) 11:1–45Google Scholar
  3. 3.
    Crabbé PA (1967) Signification du tissu lymphoide des muqueuses digestives. Arscia, BruxellesGoogle Scholar
  4. 4.
    Ferguson A, McClure JP, Townley RRW (1976) Intraepithelial lymphocyte counts in small intestinal biopsies from children with diarrhoea. Acta Paediatr Scand 64:541–546Google Scholar
  5. 5.
    Ferguson A (1977) Intraepithelial lymphocytes of the small intestine. Gut 18:921–937Google Scholar
  6. 6.
    Fluge G, Aksnes L (1981) Morphological and morphometric assessment of human duodenal biopsies maintained in organ culture. In vitro influences of gluten in coeliac disease. Scand J Gastroenterol 16:555–567Google Scholar
  7. 7.
    Granditsch G, Wick G (1975) Immunologische Studien an Kindern mit Coeliakie. Klin Pädiatr 188:408–417Google Scholar
  8. 8.
    Green F, Haworth B (1980) Immunoglobulin-containing cells in jejunal mucosa of children with protein-energy malnutrition and gastroenteritis. Arch Dis Child 55:380–383Google Scholar
  9. 9.
    Guix M, Skinner JM, Whitehead R (1979) Measuring intra-epithelial lymphocytes, surface area, and volume of lamina propria in the jejunal mucosa of coeliac patients. Gut 20:275–278Google Scholar
  10. 10.
    Howdle PD, Corazza GR, Bullen AW, Losowsky MS (1981) Gluten sensitivity of small intestinal mucosa in vitro: Quantitative assessment of histological change. Gastroenterology 80:442–450Google Scholar
  11. 11.
    Iancu T, Elian E (1976) The intestinal microvillus: ultra-structural variability in coeliac disease and cow's milk in-tolerance. Acta Paediatr Scand 65:65–73Google Scholar
  12. 12.
    Jos J, Rey J, Frézal J (1972) Etude immunohistochimique de la muqueuse intestinale chez l' enfant. I. Les syndromes de malabsorption. Arch Fr Pédiatr 29:681–698Google Scholar
  13. 13.
    Kilby A (1976) Paediatric small intestinal biopsy capsule with two ports. Gut 17:158–159Google Scholar
  14. 14.
    Kosnai I, Kuitunen P, Savilahti E, Rapola J, Köhegyi J (1980) Cell kinetics in the jejunal crypt epithelium in malabsorption syndrome with cow's milk protein intolerance and in coeliac disease of childhood. Gut 21:1041–1046Google Scholar
  15. 15.
    Kuitunen P, Rapola J, Savilahti E, Visakorpi JK (1973) Response of the jejunal mucosa to cow's milk in the malabsorption syndrome with cow's milk intolerance. A light and electron microscopic study. Acta Paediatr Scand 62:585–595Google Scholar
  16. 16.
    Lancaster-Smith M, Packer S, Kumar PJ, Harries JT (1976) Cellular infiltrate of the jejunum after re-introduction of dietary gluten in children with treated coeliac disease. J Clin Pathol 29:587–591Google Scholar
  17. 17.
    Lancaster-Smith M, Packer S, Kumar PJ, Harries JT (1976) Immunological phenomena in the jejunum and serum after re-introduction of dietary gluten in children with treated coeliac disease. J Clin Pathol 29:592–597Google Scholar
  18. 18.
    McNeish AS, Rolles CJ, Arthur LJH (1976) Criteria for diagnosis of temporary gluten intolerance. Arch Dis Child 51:275–278Google Scholar
  19. 19.
    McNicholl B, Egan-Mitchell B, Stevens F, Keane R, Baker S, McCarthy CF, Fottrell PF (1976) Mucosal recovery in treated childhood celiac disease (gluten-sensitive enteropathy). J Pediatr 89:418–424Google Scholar
  20. 20.
    Maffei HVL, Kingston D, Hill ID, Shiner M (1979) Histopathologic changes and the immune response within the jejunal mucosa in infants and children. Pediatr Res 13:733–736Google Scholar
  21. 21.
    Manuel PD, Walker-Smith JA, France NE (1979) Patchy enteropathy in childhood. Gut 20:211–215Google Scholar
  22. 22.
    Marsh MN (1980) Studies of intestinal lymphoid tissue. III. Quantitative analysis of epithelial lymphocytes in the small intestine of human control subjects and of patients with celiac sprue. Gastroenterology 79:481–492Google Scholar
  23. 23.
    Marsh MN (1981) The small intestine: mechanisms of local immunity and gluten sensitivity. Clin Sci 61:497–503Google Scholar
  24. 24.
    Marvomichalis J, Brueton MJ, McNeish AS, Anderson CM (1976) Evaluation of the intraepithelial lymphocyte count in the jejunum in childhood enteropathies. Gut 17:600–603Google Scholar
  25. 25.
    Meeuwisse G (1970) Diagnostic criteria in coeliac disease. Acta Paediatr Scand 59:461–463Google Scholar
  26. 26.
    Meinhard EA, Wadbrook DG, Risdon RA (1975) Computer card morphometry of jejunal biopsies in childhood coeliac disease. J Clin Pathol 28:85–93Google Scholar
  27. 27.
    Nie HH, Hull CH, Jenkins JG, Steinbrenner K, Bent DH (1975) SPSS Statistical package for the social sciences, 2nd edn. McGraw-Hill, New YorkGoogle Scholar
  28. 28.
    Penna FJ, Hill ID, Kingston D, Robertson K, Slavin G, Shiner M (1981) Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults. J Clin Pathol 34: 386–392Google Scholar
  29. 29.
    Perkkiö M, Savilahti E, Kuitunen P (1981) Morphometric and immunohistochemical study of jejunal biopsies from children with intestinal soy allergy. Eur J Pediatr 137:63–69Google Scholar
  30. 30.
    Phillips Ad, Rice SJ, France NE, Walker-Smith JA (1979) Small intestinal intraepithelial lymphocyte levels in cow's milk protein intolerance. Gut 20:509–512Google Scholar
  31. 31.
    Rahman NA (1978) Histometrische Untersuchungen und Zellauszählungen an der Jejunalmukosa bei florider und in Remission begriffener Cöliakie im Kindesalter. Thesis, Frankfurt/MainGoogle Scholar
  32. 32.
    Risdon RA, Keeling JW (1974) Quantitation of the histological changes found in small intestinal biopsy specimens from children with suspected coeliac disease. Gut 15:9–18Google Scholar
  33. 33.
    Rosekrans PCM, Meijer CJLM, Cornelisse CJ, van der Wal AM, Lindeman J (1980) Use of morphometry and immunohistochemistry of small intestinal biopsy specimens in the diagnosis of food allergy. J Clin Pathol 33:125–130Google Scholar
  34. 34.
    Rosekrans PCM, Meijer CJLM, Polanco I, Mearin ML, van der Wal AM, Lindeman J (1981) Long-term morphological and immunohistochemical observations on biopsy specimens of small intestine from children with gluten-sensitive enteropathy. Clin Pathol 34:138–144Google Scholar
  35. 35.
    Savilahti E (1972) Intestinal immunoglobulins in children with coeliac disease. Gut 13:958–964Google Scholar
  36. 36.
    Savilahti E (1973) Immunochemical study of the malabsorption syndrome with cow's milk intolerance. Gut 14:491–501Google Scholar
  37. 37.
    Scott H, Ek J, Baklien K, Brandtzaeg P (1980) Immuno-globulinproducing cells in jejunal mucosa of children with coeliac disease on a gluten-free diet and after gluten challenge. Scand J Gastroenterol 15:81–88Google Scholar
  38. 38.
    Selby WS, Janossy G, Jewell DP (1981) Immunohistological characterisation of intraepithelial lymphocytes of the human gastrointestinal tract. Gut 22:169–176Google Scholar
  39. 39.
    Shiner M, Ballard J, Smith Me (1975) The small intestinal mucosa in cow's milk allergy. Lancet I:136–140Google Scholar
  40. 40.
    Shiner M (1981) Ultrastructural features of allergic manifestations in the small intestine of children. Scand J Gastroenterol (Suppl 70) 16:49–64Google Scholar
  41. 41.
    Stern M (1981) Kuhmilchproteinintoleranz — Klinik und Pathogenese. Monatsschr Kinderheilkd 129:18–26Google Scholar
  42. 42.
    Stern M, Dietrich R (1982) Gliadin- and immunoglobulin-containing cells of small intestinal lamina propria in childhood coeliac disease. Eur J Pediatr (in press)Google Scholar
  43. 43.
    Vogel A (1971) Vergleichende Untersuchungen zur Morphologie der Dünndarmschleimhaut bei verschiedenen Formen des Malabsorptionssyndroms sowie bei anderen Erkrankungen. Virchow Arch Pathol Anat 352:226–245Google Scholar
  44. 44.
    Weibel ER (1963) Principles and methods for the morphometric study of the lung and other organs. Lab Invest 12:131–155Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • M. Stern
    • 1
  • R. Dietrich
    • 1
  • J. Müller
    • 1
  1. 1.Universitäts-Kinderklinik HamburgGermany
  2. 2.Harvard Medical School, Pediatric Gastroitestinal and Nutrition UnitMassachusetts General HospitalBostonUSA

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