Summary
Morphometric techniques were employed to measure (i) lamina propria volumes and (ii) the absolute numbers of neutrophils and plasma cells, of A, M and G isotype, within the lamina propria of jejunal mucosa. Mucosal specimens were obtained with a Watson capsule (a) from 5 patients with untreated coeliac disease, and again at least 3 months after starting on a gluten-free diet, and (b) from 9 control individuals.
Lamina propria volume of untreated coeliac mucosa (2.5 ± 0.17 × 106 µm3) was increased 2.3-fold (p < 0.01) above that of control mucosae (1.35 ± 0.08 · 106 µ m3). Compared with control mucosae, there was a 20-fold increase of neutrophils in untreated coeliac mucosae (p < 0.005). The total complement of all plasma cells in untreated coeliac mucosae (309) was twice that (149) of control mucosae. The populations of each isotype were also significantly increased over controls by factors of 1.6 (IgA;p < 0.05), 3.0 (IgM;p < 0.01) and 3.5 (IgG;p < 0.01). Their percentage distributions in untreated coeliac mucosae (A:M:G - 52:43:5) differed from those in control mucosae (A:M:G - 69:28:3) but were restored after treatment with a gluten-free diet.
However, when each isotype was expressed per unit volume of lamina propria, there was an apparent fall (· 1.4) in IgA cells, while the increase in IgM and IgG cells was less marked i.e. · 1.4 and · 1.5 respectively. These precise measurements explain why many previous investigators found a paradoxical fall in IgA cells because the (increased) volume of distribution of these cells was not taken into account. The importance of morphometric techniques in achieving valid cell ‘counts’ within the intestinal mucosa is thus illustrated by this study.
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References
Booth CC (1970) Enterocyte in coeliac disease. Br Med J 3:725–731
Booth CC, Peters TJ, Doe WF (1977) Immunopathology of coeliac disease. In: Immunology of the Gut, Ciba Foundation Symposium No 46 Elsevier/North Holland, Amsterdam p 329
Brandtzaeg P, Baklien K (1976) Immunohistochemical studies of the formation and epithelial transport of immunoglobulins in normal and diseased human intestinal mucosa. Scand J Gastroenterol 11 (suppl 36):5–45
Crabbe PA, Nash D, Bazin H, Eyssen H, Heremans JF (1969) Antibodies of the IgA type in intestinal plasma cells of germ-free mice after oral or parenteral immunization with ferritin. J Exp Med 130:723–738
Douglas AP, Crabbe PA, Hobbs JR (1970) Immunochemical studies of the serum, intestinal secretions and intestinal mucosa in patients with adult celiac disease and other forms of the celiac syndrome. Gastroenterology 59:414–425
Falchuk ZM, Strober W (1974) Gluten-sensitive enteropathy: synthesis of antigliadin antibody in vitro. Gut 15:947–952
Gasbarini G, Miglio F, Serra MA, Bernardi M (1974) Immunological studies of the jejunal mucosa in normal subjects and adult coeliac patients. Digestion 10:122–128
Guix M, Skinner JM, Whitehead R (1979) Measuring intraepithelial lymphocytes, surface area and volume of lamina propria in the jejunal mucosa of coeliac patients. Gut 20:275–278
Jos J, Rey J, Frezal J (1972) Etude immunohistochimique de la muquese intestinale chez l'enfant. Arch Franc Pediatr 29:681–698
Lancaster-Smith M, Kumar P, Marks R, Clark ML, Dawson AM (1974) Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis. Gut 15:371–376
McIntyre RLE, Piris J (1981) A method for the quantitation of human gastric G cell density in endoscopic biopsy specimens. J Clin Pathol 34:514–518
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 79:481–492
Marsh MN (1981) The small intestine: mechanisms of local immunity and gluten sensitivity. Clin Sci Mol Med 61:497–503
Marsh MN (1982) Studies of Intestinal Lymphoid Tissue. IV - The predictive value of raised mitotic indices among jejunal epithelial lymphocytes in the diagnosis of gluten-sensitive enteropathy. J Clin Pathol 35:517–525
Marsh MN, Haeney MR (1983) Studies of Intestinal Lymphoid Tissue. VI - Proliferative response of small intestinal epithelial lymphocytes distinguishes gluten- from non-gluteninduced enteropathy. J Clin Pathol 36:149–160
Marsh MN, Mathan M, Mathan VI (1983) Studies of Intestinal Lymphoid Tissue. VII -The secondary nature of lymphoid cell “activation” in the jejunal lesion of tropical sprue. Am J Pathol 112:302–312
Marsh MN (1983) Immunocytes, enterocytes and the lamina propria: an immunopathological framework of coeliac disease. J R Coll Phys Lond 17:205–212
Marsh MN (1984) The morphologic expression of immunologically-mediated change and injury within the human small intestinal mucosa. In: Batt RM, Lawrence TLJ (eds) Function and dysfunction of the small intestine of animals. Liverpool University Press, Liverpool, pp 167–198
Miles RE, Davy PJ (1977) On the choice of quadrats in stereology. J Microsc 110:27–36
Niazi NM (1982) A morphometric analysis of inter-epithelial lymphocytes in the small-intestinal mucosa of control subjects and in patients with coeliac disease and dermatitis herpetiformis. Thesis, Victoria University of Manchester
Pettingale KW (1971) Immunoglobulin-containing cells in the coeliac syndrome. Gut 12:291–296
Savilahti E (1972a) Intestinal immunoglobulins in children with coeliac disease. Gut 13:958–964
Savilahti E (1972b) Local immunological reaction in the small intestinal mucosa in children with the malabsorption syndrome induced by cow's milk. Acta Paediatr Scand 61:238
Scott H, Ek J, Baklien K, Brandtzaeg P (1980) Immunoglobulin-producing cells in jejunal mucosae of children with coeliac disease on a gluten-free diet and after gluten challenge. Scand J Gastroenterol 15:81–88
Soltoft J (1969) Immunoglobulin-containing cells in normal jejunal mucosa and in ulcerative colitis and regional enteritis. Scand J Gastroenterol 4:353–360
Soltoft J (1970) Immunoglobulin-containing cells in non-tropical sprue. Clin Exp Immunol 6:413–420
Soltoft J, Soeberg B (1972) Immunoglobulin-containing cells in the small intestine during acute enteritis. Gut 13:535–538
Strober W (1978) An immunological theory of gluten-sensitive enteropathy. In: McNicholl B, McCarthy CF, Fottrell PF (eds) Perspectives in coeliac disease. MTP Press, Lancaster, p 169
Webster ADB, Slavin G, Shiner M, Platts-Mills TAE, Asherson GL (1981) Coeliac disease with severe hypogammaglobulinaemia. Gut 22:153–157
Weibel ER (1979) Stereological Methods, vol 1. New York, Academic Press
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Supported by Medical Research Council Great Britain
Part of thesis submitted to Victoria University of Manchester by I. Dhesi.
University of Manchester School of Medicine
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Dhesi, I., Marsh, M.N., Kelly, C. et al. Morphometric analysis of small intestinal mucosa. Vichows Archiv A Pathol Anat 403, 173–180 (1984). https://doi.org/10.1007/BF00695233
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DOI: https://doi.org/10.1007/BF00695233