Differentiation between ulcerative colitis and Crohn’s disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells
Yoshio Sasaki,
Masanori Tanaka,
Hajime Kudo,
Yoshio Sasaki
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorMasanori Tanaka
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorHajime Kudo
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorYoshio Sasaki,
Masanori Tanaka,
Hajime Kudo,
Yoshio Sasaki
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorMasanori Tanaka
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorHajime Kudo
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this author Dr Masanori Tanaka, Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Email: [email protected]
Abstract
Mucosal biopsy criteria has limited validity in terms of discrimination between ulcerative colitis (UC) and Crohn’s disease (CD). The aim of this study was to set up quantitative immunohistochemical criteria, with a special focus on inflammatory cell distribution within individual specimens and throughout the large bowel. Quantitative evaluation was performed for the density of CD8+, CD45RO+, neutrophil elastase+, CD68+ and mast cell tryptase+ cells in affected and unaffected mucosa taken from 41 patients with UC and 61 patients with CD. Each slide was examined at the highest and lowest density fields, which were further divided into the upper and deeper half of mucosa. Multiple logistic regression analysis using 51 features as independent variables constructed a predictive equation finding the probability of UC (PUC), and the diagnostic categories were subsequently defined based on a receiver–operating characteristic curve. The analysis disclosed five significant features suggesting UC; these implied intense infiltration of CD8+ and mast cell tryptase+ cells, diffuse infiltration of neutrophil elastase+ and CD68+ cells, and continuous infiltration of CD45RO+ cells. The criteria consisted of three diagnostic categories, ‘suggestive of UC (PUC ≥ 0.7)’, ‘indeterminate (0.3 < PUC < 0.7)’, and ‘suggestive of CD (PUC ≤ 0.3)’; the criteria had values for sensitivity and specificity exceeding 95%. The immunohistochemical criteria distinguishing UC from CD may help to confirm the diagnosis in patients with ambiguous endoscopic and histological diagnosis.
References
- 1 Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H. Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn’s disease from ulcerative colitis. Scand. J. Gastroenterol. 1999; 34: 55–67.
- 2 Tanaka M, Saito H, Fukuda S, Sasaki Y, Munakata A, Kudo H. Simple mucosal biopsy criteria differentiating among Crohn disease, ulcerative colitis, and other forms of colitis: measurement of validity. Scand. J. Gastroenterol. 2000; 35: 281–286.
- 3 Le Berre N, Neresbach D, Kerbaol M et al. Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis. J. Clin. Pathol. 1995; 48: 749–753.
- 4 Surawicz CM, Haggitt RC, Husseman M, McFarland LV. Mucosal biopsy diagnosis of colitis: acute self-limited colitis and idiopathic inflammatory bowel disease. Gastroenterology 1994; 107: 755–763.
- 5 Konuma Y, Tanaka M, Saito H, Munakata A, Yoshida Y. A study of the histological criteria for ulcerative colitis: retrospective evaluation of multiple colonic biopsies. J. Gastroenterol. 1995; 30: 189–194.
- 6 Seldenrijk CA, Morson BC, Meuwissen SGM, Schipper NW, Lindeman J, Meijer CJLM. Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: diagnostic implications. Gut 1991; 32: 1514–1520.
- 7 Morson BC. Rectal and colonic biopsy in inflammatory bowel disease. Am. J. Gastroenterol. 1977; 67: 417–426.
- 8 Nostrant TT, Kumar Appelman HD. Histopathology differentiates acute self-limited colitis from ulcerative colitis. Gastroenterology 1987; 92: 318–328.
- 9 Theodossi A, Spiegelhalter DJ, Jass J et al. Observer variation and discriminatory value of biopsy features in inflammatory bowel disease. Gut 1994; 35: 961–968.
- 10 Schmitz-Moormann P, Himmelmann GW. Does quantitative histology of rectal biopsy improve the differential diagnosis of Crohn’s disease and ulcerative colitis in adults? Pathol. Res. Pract. 1988; 183: 481–488.
- 11 Caballero T, Nogueras F, Medina MT et al. Intraepithelial and lamina propria leucocyte subsets in inflammatory bowel disease: an immunohistochemical study of colon and rectal biopsy specimens. J. Clin. Pathol. 1995; 48: 743–748.
- 12 Allison MC, Poulter LW, Dhillon AP, Pounder RE. Immunohistological studies of surface antigen on colonic lymphoid cells in normal and inflamed mucosa. Comparison of follicular and lamina propria lymphocytes. Gastroenterology 1990; 99: 421–430.
- 13 Selby WS, Janossy G, Bofill M, Jewell DP. Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques. Gut 1984; 25: 32–40.
- 14 Hirata I, Berrebi G, Austin LL, Keren DF, Dobbins WO III. Immunohistological characterization of intraepithelial and lamina propria lymphocytes in control ileum and colon and in inflammatory bowel disease. Dig. Dis. Sci. 1986; 31: 593–603.
- 15 Deusch K, Reich K. Immunological aspects of inflammatory bowel disease. Endoscopy 1992; 24: 568–577.
- 16 Burgio VL, Fais S, Boirivant M, Perrone A, Pallone F. Peripheral monocyte and naive T-cell recruitment and activation in Crohn’s disease. Gastroenterology 1995; 109: 1029–1038.
- 17 Lee HB, Kim HK, Yim CY, Kim DG, Ahn DS. Differences in immunophenotyping of lymphocytes between ulcerative colitis and Crohn’s disease. Korean J. Intern. Med. 1997; 12: 7–15.
- 18 Senju M, Wu KC, Mahida YR, Jewell DP. Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn’s disease. Dig. Dis. Sci. 1990; 36: 1453–1458.
- 19
Oshitani N,
Campbell A,
Kitano A,
Kobayashi K,
Jewell DP.
In situ comparison of phenotypical and functional activity of inflating cells in ulcerative colitis mucosa.
J. Pathol.
1996; 178: 95–99.DOI: 10.1002/(SICI)1096-9896(199601)178:1<95::AID-PATH402>3.3.CO;2-G
10.1002/(SICI)1096-9896(199601)178:1<95::AID-PATH402>3.0.CO;2-P PubMed Web of Science® Google Scholar
- 20 Morise K, Yamaguchi T, Kuroiwa A et al. Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn’s disease: an immunocytochemical study. J. Gastroenterol. 1994; 29: 257–264.
- 21 Seldenrijk CA, Drexhage HA, Meuwissen SGM, Pals ST, Meijer CJLM. Dendritic cells and scavenger macrophages in chronic inflammatory bowel disease. Gut 1989; 30: 484–491.
- 22 Allison MC, Cornwall S, Poulter LW, Dhillon AP, Pounder RE. Macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease. Gut 1988; 29: 1531–1538.
- 23 Mahida YR, Patel S, Gionchetti P, Vaux D, Jewell DP. Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum. Gut 1989; 30: 826–834.
- 24 Rugtveit J, Brandtzaeg P, Halstensen TS, Fausa O, Scott H. Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut 1994; 35: 669–674.
- 25 D’Incà R, Sturniolo GC, Martines D et al. Functional and morphological changes in small bowel of Crohn’s disease patients. Influence of site of disease. Dig. Dis. Sci. 1995; 40: 1388–1393.
- 26 Thompson H, Buchmann P. Mast-cell population in rectal biopsies from patients with Crohn’s disease. In: Pepys J, Edwards AM, eds. The Mast Cell: Its Role in Health and Disease. Pitman Medical, Davos, 1979; 697–701.
- 27 Goldsmith P, McGarity B, Walls AF, Church MK, Millward-Sadler GH, Robertson DAF. Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Dig. Dis. Sci. 1990; 35: 1409–1413.
- 28 Sarin SK, Malhotra V, Sen Gupta S, Kaol A, Gaur SK, Anand BS. Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study. Dig. Dis. Sci. 1987; 32: 363–367.
- 29 Balázs M, Illyés G, Vadász G. Mast cells in ulcerative colitis. Quantitative and ultrastructural studies. Virchows Arch. B 1989; 57: 353–360.
- 30 Dvorak AM, Monahan RA. Crohn’s disease-mast cell quantitation using one micron plastic sections for light microscopic study. Pathol. Annu. 1983; 18: 181–190.
- 31 Hiatt RB, Katz L. Mast cells in inflammatory conditions of the gastrointestinal tract. Am. J. Gastroenterol. 1962; 37: 541–545.
- 32 King T, Biddle W, Bhatia P, Moore J, Miner PB Jr. Colonic mucosal mast cell distribution at line of demarcation of active ulcerative colitis. Dig. Dis. Sci. 1992; 37: 490–495.
- 33 Yamagata K, Tanaka M, Kudo H. A quantitative immunohistochemical evaluation of inflammatory cells at the affected and unaffected sites of inflammatory bowel disease. J. Gastroenterol. Hepatol. 1998; 13: 801–808.
- 34 Shivananda S, Hordijk ML, Ten Kate FJW, Probert CSJ, Mayberry JF. Differential diagnosis of inflammatory bowel disease. A comparison of various diagnostic classifications. Scand. J. Gastroenterol. 1991; 26: 167–173.
- 35 Lennard-Jones JE. Classification of inflammatory bowel disease. Scand. J. Gastroenterol. 1989; 24: 2–6.
- 36 Hsu SM, Raine L, Franger H. The use of antiavidin antibody and avidin-biotin peroxidase complex in immunoperoxidase techniques. Am. J. Clin. Pathol. 1981; 75: 816–821.
- 37 Dundas SAC, Dutton J, Skipworth P. Reliability of rectal biopsy in distinguishing between chronic inflammatory bowel disease and acute self-limiting colitis. Histopathology 1997; 31: 60–66.
- 38 Mason DY, Cordel JL, Gaulard P, Tse AGD, Brown MH. Immunohistological detection of human cytotoxic/suppressor T cells using antibodies to a CD8 peptide sequence. J. Clin. Pathol. 1992; 45: 1084–1088.
- 39 Pulford KAF, Erber EN, Crick JA et al. Use of monoclonal antibody against human neutrophil elastase in normal and leukaemic myeloid cells. J. Clin. Pathol. 1988; 41: 853–860.
- 40 Dewald B, Rindler-Ludwig R, Bretz U, Baggiolini M. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J. Exp. Med. 1975; 141: 709–723.
- 41 Falini B, Flenghi L, Pileri S et al. PG-M1: a new monoclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule. Am. J. Pathol. 1993; 142: 1359–1372.
- 42 Walls AF, Jones DB, Williams JH, Church MK, Holgate ST. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J. Pathol. 1990; 162: 119–126.
- 43 Morimoto C. CD45 cluster report. In: Schlossman SF, Bounasell L, Gilks W et al., eds. Leukocyte Typing V. White Cell Differentiation Antigens. Proceeding of the Fifth International Workshop and Conference, 3–7 November, 1993. Oxford University Press, Boston, 1995; 386–389.
- 44 Poppema S, Lai R, Visser L. Monoclonal antibody OPD4 is reactive with CD45RO, but differs from UCHL1 by the absence of monocyte reactivity. Am. J. Pathol. 1991; 139: 725–729.
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