Rosenberg W M, Prince C, Kaklamanis L, Fox S B, Jackson D G, Simmons D L, Chapman R W, Trowell J M, Jewell D P, Bell J I
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK.
Lancet. 1995 May 13;345(8959):1205-9. doi: 10.1016/s0140-6736(95)91991-0.
Immune mechanisms, possibly involving cell-surface molecules such as CD44, have been invoked to explain the pathogenesis of inflammatory bowel disease. We used monoclonal antibodies against epitopes encoded within the variable region of CD44 to investigate CD44 isoform expression in colon, small intestine, and liver in patients with various intestinal disorders and in controls. Biopsy samples from patients with ulcerative colitis showed significantly increased epithelial expression of CD44 isoforms containing the v6 and v3 epitopes, detected with antibodies 2F10 and 3G5, respectively. CD44v6 was detected on colonic crypt epithelial cells in 23 of 25 ulcerative colitis samples compared with 3 of 18 colonic Crohn's disease samples (p = 3.0 x 10(-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 < 1 x 10(-8); odds ratio 199 [25.5-2294]). No significant expression of CD44v6, CD44v3, or CD44v8/9 was found in samples of normal proximal colon from 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 small-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 isoforms 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.
免疫机制，可能涉及诸如CD44等细胞表面分子，已被用于解释炎症性肠病的发病机制。我们使用针对CD44可变区内编码表位的单克隆抗体，来研究患有各种肠道疾病的患者及对照组的结肠、小肠和肝脏中CD44异构体的表达情况。溃疡性结肠炎患者的活检样本显示，分别用抗体2F10和3G5检测到的含有v6和v3表位的CD44异构体的上皮表达显著增加。在25例溃疡性结肠炎样本中的23例结肠隐窝上皮细胞上检测到CD44v6，而在18例结肠克罗恩病样本中的3例以及52例对照组（22例正常结肠、10例感染性结肠炎、2例放射性结肠炎和18例结肠克罗恩病）中的3例检测到（p = 3.0×10⁻⁶；优势比57.5 [95%可信区间6.83 - 702]）。在4例远端溃疡性结肠炎患者的正常近端结肠样本中未发现CD44v6、CD44v3或CD44v8/9的显著表达，而来自病变区域的样本显示有CD44v6和CD44v3染色。在15例正常小肠样本、11例小肠袋炎样本、8例乳糜泻样本、3例小肠克罗恩病样本、6例正常肝脏样本、6例原发性胆汁性肝硬化样本或9例原发性硬化性胆管炎样本中未发现CD44变体的表达。溃疡性结肠炎中隐窝上皮细胞上CD44v6和v3表位的高表达强度表明，CD44异构体可能在溃疡性结肠炎中起重要作用。它们的检测在区分溃疡性结肠炎与包括克罗恩病在内的其他形式的结肠炎症方面可能具有诊断潜力。
