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Anti-TCR gamma antibody in celiac disease: the value of count on formalin-fixed paraffin-embedded biopsies.

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Abstract

Small bowel intraepithelial lymphocytosis (IL) may depend from different causes, including celiac disease (CD). Demonstration of increased number of duodenal T cell receptor gamma-delta (TCRγδ) positive intraepithelial lymphocytes (IELs) has been used to support CD diagnosis on frozen material. This work evaluates a new commercially available anti-TCRγ antibody on formalin-fixed paraffin embedded (FFPE) small bowel biopsies. Anti-CD3 and anti-TCR CγM1 (clone γ3.20) from Thermo Scientific were applied by immunohistochemistry on 59 FFPE biopsies from 18 cases of CD with mild/severe atrophy, 19 cases of IL in CD patients on gluten-free diet (IL-GFD), 14 cases of IL (6/14 with positive CD-related serology), and 8 controls (CTR) with mild duodenitis and negative CD serology and genotyping. IELs/100 epithelial cells were counted in at least six high power fields. CD3+ and TCRγ+ IELs were significantly higher in CD, IL-GFD, and IL compared with CTR, but in contrast to CD3+ IELs, TCRγ+ IELs were significantly increased in CD and IL-GFD compared with IL. Furthermore, TCRγ+ IELs discriminated between IL with negative and positive CD-related serology (p = 0.02). TCRγ+ IELs can be identified on FFPE samples and their evaluation adds useful information for the work-up of small bowel biopsies in CD diagnosis. In fact, TCRγ staining coupled with CD3, may represent an additional tool to recognize cases of latent/potential CD when serology and clinical data are not conclusive or when the histological diagnosis remains equivocal.

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References

  1. Ferguson A (1977) Intraepithelial lymphocytes of the small intestine. Gut 18(11):921–937

    Article  PubMed  CAS  Google Scholar 

  2. Veress B, Franzen L, Bodin L, Borch K (2004) Duodenal intraepithelial lymphocyte-count revisited. Scand J Gastroenterol 39(2):138–144

    Article  PubMed  CAS  Google Scholar 

  3. Hayat M, Cairns A, Dixon MF, O'Mahony S (2002) Quantitation of intraepithelial lymphocytes in human duodenum: what is normal? J Clin Pathol 55(5):393–394

    Article  PubMed  CAS  Google Scholar 

  4. Brown I, Mino-Kenudson M, Deshpande V, Lauwers GY (2006) Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis. Arch Pathol Lab Med 130(7):1020–1025

    PubMed  Google Scholar 

  5. Maki M, Holm K, Collin P, Savilahti E (1991) Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease. Gut 32(11):1412–1414

    Article  PubMed  CAS  Google Scholar 

  6. Holm K, Maki M, Savilahti E, Lipsanen V, Laippala P, Koskimies S (1992) Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease. Lancet 339(8808):1500–1503

    Article  PubMed  CAS  Google Scholar 

  7. Arranz E, Bode J, Kingstone K, Ferguson A (1994) Intestinal antibody pattern of coeliac disease: association with gamma/delta T cell receptor expression by intraepithelial lymphocytes, and other indices of potential coeliac disease. Gut 35(4):476–482

    Article  PubMed  CAS  Google Scholar 

  8. Halstensen TS, Scott H, Brandtzaeg P (1989) 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 30(6):665–672

    Article  PubMed  CAS  Google Scholar 

  9. Jarvinen TT, Kaukinen K, Laurila K, Kyronpalo S, Rasmussen M, Maki M, Korhonen H, Reunala T, Collin P (2003) Intraepithelial lymphocytes in celiac disease. Am J Gastroenterol 98(6):1332–1337

    Article  PubMed  Google Scholar 

  10. Kutlu T, Brousse N, Rambaud C, Le Deist F, Schmitz J, Cerf-Bensussan N (1993) 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 34(2):208–214

    Article  PubMed  CAS  Google Scholar 

  11. Halstensen TS, Farstad IN, Scott H, Fausa O, Brandtzaeg P (1990) Intraepithelial TcR alpha/beta+ lymphocytes express CD45RO more often than the TcR gamma/delta+ counterparts in coeliac disease. Immunology 71(4):460–466

    PubMed  CAS  Google Scholar 

  12. Savilahti E, Arato A, Verkasalo M (1990) Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease. Pediatr Res 28(6):579–581

    Article  PubMed  CAS  Google Scholar 

  13. Volta U, Villanacci V (2011) Celiac disease: diagnostic criteria in progress. Cell Mol Immunol 8(2):96–102

    Article  PubMed  CAS  Google Scholar 

  14. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Carteni M, Riegler G, de Magistris L, Fasano A (2011) Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC medicine 9:23. doi:10.1186/1741-7015-9-23

    Article  PubMed  CAS  Google Scholar 

  15. Paparo F, Petrone E, Tosco A, Maglio M, Borrelli M, Salvati VM, Miele E, Greco L, Auricchio S, Troncone R (2005) Clinical, HLA, and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa. Am J Gastroenterol 100(10):2294–2298

    Article  PubMed  Google Scholar 

  16. Kakar S, Nehra V, Murray JA, Dayharsh GA, Burgart LJ (2003) Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol 98(9):2027–2033

    Article  PubMed  Google Scholar 

  17. Rodriguez-Pinilla SM, Ortiz-Romero PL, Monsalvez V, Tomas IE, Almagro M, Sevilla A, Camacho G, Longo MI, Pulpillo A, Diaz-Perez JA, Montes-Moreno S, Castro Y, Echevarria B, Trebol I, Gonzalez C, Sanchez L, Otin AP, Requena L, Rodriguez-Peralto JL, Cerroni L, Piris MA (2013) TCR-gamma expression in primary cutaneous T-cell lymphomas. Am J Surg Pathol 37(3):375–384

    Article  PubMed  Google Scholar 

  18. Bizzaro N, Villalta D, Tonutti E, Doria A, Tampoia M, Bassetti D, Tozzoli R (2003) IgA and IgG tissue transglutaminase antibody prevalence and clinical significance in connective tissue diseases, inflammatory bowel disease, and primary biliary cirrhosis. Dig Dis Sci 48(12):2360–2365

    Article  PubMed  CAS  Google Scholar 

  19. Carroccio A, Di Prima L, Falci C, Le Moli C, Soresi M, Montalto G, Notarbartolo A (2002) Predictive value of serological tests in the diagnosis of celiac disease. Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna 17(2):102–107

    Google Scholar 

  20. Leffler DA, Schuppan D (2010) Update on serologic testing in celiac disease. Am J Gastroenterol 105(12):2520–2524

    Article  PubMed  Google Scholar 

  21. Stern M, Working Group on Serologic Screening for Celiac D (2000) Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization. J Pediatr Gastroenterol Nutr 31(5):513–519

    Article  Google Scholar 

  22. Villanacci V, Ceppa P, Tavani E, Vindigni C, Volta U, Gruppo Italiano Patologi Apparato D, Societa Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology Id (2011) Coeliac disease: the histology report. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 43(Suppl 4):S385–395

    Article  Google Scholar 

  23. Maki M, Holm K, Lipsanen V, Hallstrom O, Viander M, Collin P, Savilahti E, Koskimies S (1991) Serological markers and HLA genes among healthy first-degree relatives of patients with coeliac disease. Lancet 338(8779):1350–1353

    Article  PubMed  CAS  Google Scholar 

  24. Savilahti E, Reunala T, Maki M (1992) Increase of lymphocytes bearing the gamma/delta T cell receptor in the jejunum of patients with dermatitis herpetiformis. Gut 33(2):206–211

    Article  PubMed  CAS  Google Scholar 

  25. Eiras P, Roldan E, Camarero C, Olivares F, Bootello A, Roy G (1998) Flow cytometry description of a novel CD3-/CD7+ intraepithelial lymphocyte subset in human duodenal biopsies: potential diagnostic value in coeliac disease. Cytometry 34(2):95–102

    Article  PubMed  CAS  Google Scholar 

  26. Camarero C, Eiras P, Asensio A, Leon F, Olivares F, Escobar H, Roy G (2000) Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3-/CD7+ and T cell receptor gammadelta subsets studied by flow cytometry. Acta paediatrica 89(3):285–290

    PubMed  CAS  Google Scholar 

  27. Kokkonen J, Holm K, Karttunen TJ, Maki M (2000) Children with untreated food allergy express a relative increment in the density of duodenal gammadelta+ T cells. Scand J Gastroenterol 35(11):1137–1142

    Article  PubMed  CAS  Google Scholar 

  28. Spencer J, Isaacson PG, MacDonald TT, Thomas AJ, Walker-Smith JA (1991) Gamma/delta T cells and the diagnosis of coeliac disease. Clin Exp Immunol 85(1):109–113

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

SL is supported by “Borsa di studio Prof Roberto Tosoni” (Garda Vita, BCC del Garda). All authors approved the final version of the article, including the authorship list.

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The authors declare no competing financial interests.

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Correspondence to Silvia Lonardi.

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Lonardi, S., Villanacci, V., Lorenzi, L. et al. Anti-TCR gamma antibody in celiac disease: the value of count on formalin-fixed paraffin-embedded biopsies.. Virchows Arch 463, 409–413 (2013). https://doi.org/10.1007/s00428-013-1448-7

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  • DOI: https://doi.org/10.1007/s00428-013-1448-7

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