INCREASED EXPRESSION OF CD44V6 AND CD44V3 IN ULCERATIVE-COLITIS BUT NOT COLONIC CROHNS-DISEASE

Immune mechanisms, possibly involving cell-surface molecules such as C D44, have been invoked to explain the pathogenesis of inflammatory bow el disease. We used monoclonal antibodies against epitopes encoded wit hin the variable region of CD44 to investigate CD44 isoform expression in colon, small intestine, and liver in patients with various intesti nal disorders and in controls. Biopsy samples from patients with ulcer ative colitis showed significantly increased epithelial expression of CD44 isoforms containing the v6 and v3 epitopes, detected with antibod ies 2F10 and 3G5, respectively. CD44v6 was detected on colonic crypt e pithelial cells in 23 of 25 ulcerative colitis samples compared with 3 of 18 colonic Crohn's disease samples (p=3.0x10(-6); odds ratio 57.5 [95% CI 6.83-702]) and 3 of 52 controls (22 normal colon, 10 infective colitis, 2 radiation colitis, and 18 colonic Crohn's disease; p<1x10( -8); odds ratio 199 [25.5-2294]). No significant expression of CD44v6, CD44v3, or CD44v8/9 was found in samples of normal proximal colon fro m 4 patients with distal ulcerative colitis, whereas samples from the affected area showed staining for CD44v6 and CD44v3. No expression of CD44 variants was found in 15 samples of normal small intestine, 11 sm all-bowel pouchitis, 8 coeliac disease, 3 small-bowel Crohn's disease, 6 normal liver, 6 primary biliary cirrhosis, or 9 primary sclerosing cholangitis. The high intensity of CD44v6 and v3 epitope expression on crypt epithelial cells in ulcerative colitis suggests that CD44 isofo rms may have an important role in ulcerative colitis. Their detection could have diagnostic potential in differentiating ulcerative colitis from other forms of colonic inflammation including Crohn's disease.