Skip to main content
NCBI home page
Gut logoLink to Gut
. 1995 Oct;37(4):519–523. doi: 10.1136/gut.37.4.519

Immunohistochemical findings in jejunal specimens from patients with IgA deficiency.

T Klemola 1, E Savilahti 1, A Arato 1, T Ormälä 1, J Partanen 1, C Eland 1, S Koskimies 1
PMCID: PMC1382904  PMID: 7489939

Abstract

Jejunal biopsy specimens from 25 patients with IgA deficiency (IgAd) were studied immunohistochemically to find markers of inflammation. Five of the 25 patients had coeliac disease (CD): they were on a gluten free diet and had normal jejunal morphology. Only two of 15 specimens from control subjects had CD25+ cells in the surface epithelium, while this was seen in 19 out of 20 specimens from IgAd patients (p < 0.0001). A significant increase of CD25+ cells was also noted in the lamina propria of IgAd patients. The median percentage of crypt cells in mitosis (Ki67+ cells) was higher in the specimens from IgAd patients (26%) than in those from controls (13%, p < 0.001). The densities of gamma delta T cell receptor positive cells in the surface epithelium and lamina propria did not differ in the specimens from IgAd patients and those of controls nor was the expression of HLA class II antigens augmented in the surface epithelium. These findings were similar for the IgAd patients whether or not the patient had DQB 0201 allele, a genetic marker which is strongly associated with CD. The inadequacy of the local immunoglobulins in patients with IgAd may lead to increased T cell activation, which is accompanied by the appearance of intraepithelial CD25+ cells and with an increase in the mitotic rate in the crypts.

Full text

PDF
519

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaud-Battandier F., Cerf-Bensussan N., Amsellem R., Schmitz J. Increased HLA-DR expression by enterocytes in children with celiac disease. Gastroenterology. 1986 Nov;91(5):1206–1212. doi: 10.1016/s0016-5085(86)80018-x. [DOI] [PubMed] [Google Scholar]
  2. Aukrust P., Frøland S. S., Müller F. Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features. Clin Exp Immunol. 1992 Aug;89(2):211–216. doi: 10.1111/j.1365-2249.1992.tb06934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brandtzaeg P., Fjellanger I., Gjeruldsen S. T. Immunoglobulin M: local synthesis and selective secretion in patients with immunoglobulin A deficiency. Science. 1968 May 17;160(3829):789–791. doi: 10.1126/science.160.3829.789. [DOI] [PubMed] [Google Scholar]
  4. Brandtzaeg P., Gjeruldsen S. T., Korsrud F., Baklien K., Berdal P., Ek J. The human secretory immune system shows striking heterogeneity with regard to involvement of J chain-positive IgD immunocytes. J Immunol. 1979 Feb;122(2):503–510. [PubMed] [Google Scholar]
  5. Buckley R. H., Dees S. C. Correlation of milk precipitins with IgA deficiency. N Engl J Med. 1969 Aug 28;281(9):465–469. doi: 10.1056/NEJM196908282810903. [DOI] [PubMed] [Google Scholar]
  6. Cunningham-Rundles C., Brandeis W. E., Good R. A., Day N. K. Bovine antigens and the formation of circulating immune complexes in selective immunoglobulin A deficiency. J Clin Invest. 1979 Jul;64(1):272–279. doi: 10.1172/JCI109448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cunningham-Rundles C., Brandeis W. E., Good R. A., Day N. K. Milk precipitins, circulating immune complexes, and IgA deficiency. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3387–3389. doi: 10.1073/pnas.75.7.3387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Friman V., Quiding M., Czerkinsky C., Nordström I., Larsson L., Ericson D., Björkander J., Theman K., Kilander A., Holmgren J. Intestinal and circulating antibody-forming cells in IgA-deficient individuals after oral cholera vaccination. Clin Exp Immunol. 1994 Feb;95(2):222–226. doi: 10.1111/j.1365-2249.1994.tb06514.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Giorgi P. L., Catassi C., Sbarbati A., Bearzi I., Cinti S. Ultrastructural findings in the jejunal mucosa of children with IgA deficiency. J Pediatr Gastroenterol Nutr. 1986 Nov-Dec;5(6):892–898. doi: 10.1097/00005176-198611000-00012. [DOI] [PubMed] [Google Scholar]
  10. Halstensen T. S., Scott H., Brandtzaeg P. Intraepithelial T cells of the TcR gamma/delta+ CD8- and V delta 1/J delta 1+ phenotypes are increased in coeliac disease. Scand J Immunol. 1989 Dec;30(6):665–672. doi: 10.1111/j.1365-3083.1989.tb02474.x. [DOI] [PubMed] [Google Scholar]
  11. Holm K., Mäki M., Savilahti E., Lipsanen V., Laippala P., Koskimies S. Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease. Lancet. 1992 Jun 20;339(8808):1500–1503. doi: 10.1016/0140-6736(92)91262-7. [DOI] [PubMed] [Google Scholar]
  12. Holm K., Savilahti E., Koskimies S., Lipsanen V., Mäki M. Immunohistochemical changes in the jejunum in first degree relatives of patients with coeliac disease and the coeliac disease marker DQ genes. HLA class II antigen expression, interleukin-2 receptor positive cells and dividing crypt cells. Gut. 1994 Jan;35(1):55–60. doi: 10.1136/gut.35.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kelly J., O'Farrelly C., O'Mahony C., Weir D. G., Feighery C. Immunoperoxidase demonstration of the cellular composition of the normal and coeliac small bowel. Clin Exp Immunol. 1987 Apr;68(1):177–188. [PMC free article] [PubMed] [Google Scholar]
  14. Klemola T. Immunohistochemical findings in the intestine of IgA-deficient persons: number of intraepithelial T lymphocytes is increased. J Pediatr Gastroenterol Nutr. 1988 Jul-Aug;7(4):537–543. doi: 10.1097/00005176-198807000-00010. [DOI] [PubMed] [Google Scholar]
  15. Kutlu T., Brousse N., Rambaud C., Le Deist F., Schmitz J., Cerf-Bensussan N. Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. Gut. 1993 Feb;34(2):208–214. doi: 10.1136/gut.34.2.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MacDonald T. T., Spencer J. Cell-mediated immune injury in the intestine. Gastroenterol Clin North Am. 1992 Jun;21(2):367–386. [PubMed] [Google Scholar]
  17. MacDonald T. T., Spencer J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J Exp Med. 1988 Apr 1;167(4):1341–1349. doi: 10.1084/jem.167.4.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MacDonald T. T. The role of activated T lymphocytes in gastrointestinal disease. Clin Exp Allergy. 1990 May;20(3):247–252. doi: 10.1111/j.1365-2222.1990.tb02679.x. [DOI] [PubMed] [Google Scholar]
  19. Marley N. J., Macartney J. C., Ciclitira P. J. HLA-DR, DP and DQ expression in the small intestine of patients with coeliac disease. Clin Exp Immunol. 1987 Nov;70(2):386–393. [PMC free article] [PubMed] [Google Scholar]
  20. Mäki M., Holm K., Collin P., Savilahti E. Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease. Gut. 1991 Nov;32(11):1412–1414. doi: 10.1136/gut.32.11.1412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nilssen D. E., Aukrust P., Frøland S. S., Müller F., Fausa O., Halstensen T. S., Brandtzaeg P. Duodenal intraepithelial gamma/delta T cells and soluble CD8, neopterin, and beta 2-microglobulin in serum of IgA-deficient subjects with or without IgG subclass deficiency. Clin Exp Immunol. 1993 Oct;94(1):91–98. doi: 10.1111/j.1365-2249.1993.tb05983.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. North M. E., Spickett G. P., Webster A. D., Farrant J. Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. Clin Exp Immunol. 1991 Nov;86(2):252–255. doi: 10.1111/j.1365-2249.1991.tb05805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Olerup O., Smith C. I., Hammarström L. Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. Nature. 1990 Sep 20;347(6290):289–290. doi: 10.1038/347289a0. [DOI] [PubMed] [Google Scholar]
  24. Roep B. O., Bontrop R. E., Peña A. S., van Eggermond M. C., van Rood J. J., Giphart M. J. An HLA-DQ alpha allele identified at DNA and protein level is strongly associated with celiac disease. Hum Immunol. 1988 Dec;23(4):271–279. doi: 10.1016/0198-8859(88)90062-6. [DOI] [PubMed] [Google Scholar]
  25. Russell G. J., Winter H. S., Fox V. L., Bhan A. K. Lymphocytes bearing the gamma delta T-cell receptor in normal human intestine and celiac disease. Hum Pathol. 1991 Jul;22(7):690–694. doi: 10.1016/0046-8177(91)90291-v. [DOI] [PubMed] [Google Scholar]
  26. Savilahti E., Arato A., Verkasalo M. Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease. Pediatr Res. 1990 Dec;28(6):579–581. doi: 10.1203/00006450-199012000-00005. [DOI] [PubMed] [Google Scholar]
  27. Savilahti E. IgA deficiency in children. Immunoglobulin-containing cells in the intestinal mucosa, immunoglobulins in secretions and serum IgA levels. Clin Exp Immunol. 1973 Mar;13(3):395–406. [PMC free article] [PubMed] [Google Scholar]
  28. Savilahti E., Klemola T., Carlsson B., Mellander L., Stenvik M., Hovi T. Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged. J Clin Immunol. 1988 Mar;8(2):89–94. doi: 10.1007/BF00917895. [DOI] [PubMed] [Google Scholar]
  29. Savilahti E., Pelkonen P., Verkasalo M., Koskimies S. Selective deficiency of immunoglobulin A in children. Klin Padiatr. 1985 Jul-Aug;197(4):336–340. doi: 10.1055/s-2008-1033999. [DOI] [PubMed] [Google Scholar]
  30. Scott H., Brandtzaeg P., Solheim B. G., Thorsby E. Relation between HLA-DR-like antigens and secretory component (SC) in jejunal epithelium of patients with coeliac disease or dermatitis herpetiformis. Clin Exp Immunol. 1981 May;44(2):233–238. [PMC free article] [PubMed] [Google Scholar]
  31. Sollid L. M., Markussen G., Ek J., Gjerde H., Vartdal F., Thorsby E. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med. 1989 Jan 1;169(1):345–350. doi: 10.1084/jem.169.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Spencer J., Isaacson P. G., Diss T. C., MacDonald T. T. Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer in human intestinal intraepithelial lymphocytes. Eur J Immunol. 1989 Jul;19(7):1335–1338. doi: 10.1002/eji.1830190728. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES