Hirata Naoto, Oshitani Nobuhide, Kamata Noriko, Sogawa Mitsue, Yamagami Hirokazu, Watanabe Kenji, Watanabe Toshio, Tominaga Kazunari, Fujiwara Yasuhiro, Maeda Kiyoshi, Hirakawa Kosei, Arakawa Tetsuo
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Inflamm Bowel Dis. 2008 Aug;14(8):1084-90. doi: 10.1002/ibd.20447.
Pouchitis is the most common complication of restorative proctocolectomy in patients with ulcerative colitis (UC). The etiology of pouchitis is not known. We have previously reported the specific and significant proliferation of immature plasma lineage cells in the ulcer bases and inflamed mucosa of UC. In the present study we report the results of a phenotypic study of ileal pouch mucosa.
Biopsy samples were taken from the ileal pouch of 22 patients with UC (12 with pouchitis, 10 with a normal pouch) and 5 patients with familial adenomatous polyposis (FAP) (with a normal pouch) who underwent restorative proctocolectomy, and normal ileum of 10 patients with UC yet to undergo pouch surgery. Frozen sections were cut from fixed samples and reacted with various lymphocyte markers and anti-Ki-67 antibodies. Ki-67+ cells, CD19+ cells, and CD138+ cells were significantly increased in the pouchitis mucosa of patients with UC.
Immunological double staining revealed significantly increased numbers of CD19+Ki-67+ cells and CD138+Ki-67+ cells in the pouchitis mucosa of patients with UC compared to noninflamed UC pouch, FAP pouch, and normal ileum of UC patients. The number of CD19+CD138+ cells was significantly increased in inflamed pouch mucosa. The increased number of CD19+CD138+ cells we observed represents proliferation of immature plasma cells. Moreover, the increase in labeling for Ki-67 among CD19 cells and CD138 cells suggests proliferative activity of these cells, consistent with their immaturity.
Proliferation of these immature plasma cells suggests the possibility of involvement of UC-derived abnormality in the pathogenesis of pouchitis.
袋炎是溃疡性结肠炎(UC)患者行结直肠切除术后最常见的并发症。袋炎的病因尚不清楚。我们之前报道过UC溃疡底部和炎症黏膜中未成熟浆细胞系的特异性显著增殖。在本研究中,我们报告了回肠袋黏膜表型研究的结果。
从22例UC患者(12例有袋炎,10例袋正常)、5例家族性腺瘤性息肉病(FAP)患者(袋正常)行结直肠切除术后的回肠袋以及10例尚未行袋手术的UC患者的正常回肠中获取活检样本。从固定样本中切取冰冻切片,与各种淋巴细胞标志物和抗Ki-67抗体反应。UC患者袋炎黏膜中的Ki-67+细胞、CD19+细胞和CD138+细胞显著增加。
免疫双染显示,与未发炎的UC袋、FAP袋以及UC患者的正常回肠相比,UC患者袋炎黏膜中CD19+Ki-67+细胞和CD138+Ki-67+细胞的数量显著增加。发炎袋黏膜中CD19+CD138+细胞的数量显著增加。我们观察到的CD19+CD138+细胞数量增加代表未成熟浆细胞的增殖。此外,CD19细胞和CD138细胞中Ki-67标记的增加表明这些细胞的增殖活性,与其未成熟状态一致。
这些未成熟浆细胞的增殖提示UC衍生的异常可能参与了袋炎的发病机制。