Thoree V C, Golby S J C, Boursier L, Hackett M, Dunn-Walters D K, Sanderson J D, Spencer J
Department of Gastroenterology, St Thomas' Hospital, Lambeth Palace Rd, London SE1 7EH, UK.
Gut. 2002 Jul;51(1):44-50. doi: 10.1136/gut.51.1.44.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which the colonic mucosa is infiltrated with plasma cells producing IgG autoantibodies. It is not known whether this represents a local mucosal response which has switched to IgG or a peripheral response which may have been initiated by peripheral antigen which homed to the colonic mucosa. The clonal distribution of IgG secreting cells and isotype switched variants in UC is not known.
To investigate the clonal distribution of mucosal IgG in UC and to search for related IgG and IgA secreting cells in normal and diseased mucosa and blood in UC. To investigate characteristics which may discriminate between the mucosal and peripheral repertoire in the normal mucosa and in UC.
Blood and normal and diseased mucosa from two patients with UC were studied.
Immunoglobulin gene analysis and clone specific polymerase chain reaction were used to study the clonal distribution and characteristics of IgG and related IgA in the mucosa and blood of patients with UC.
The IgG response in the mucosa of UC patients included widespread clones of cells that were present in both the diseased mucosa and blood but that were scarce in normal mucosa. Clonally related IgA class switch variants, all IgA1, were detected but also only in the diseased mucosa and blood. This suggests that these clones home preferentially to the diseased mucosa. We showed that J(H)1 usage was characteristic of the peripheral repertoire, and that examples of J(H)1 usage were observed in mucosal IgG in UC.
Overall, these data are consistent with a model of UC in which a peripheral response is expressed and expanded in the colonic mucosa.
溃疡性结肠炎(UC)是一种慢性炎症性肠病,结肠黏膜中有产生IgG自身抗体的浆细胞浸润。目前尚不清楚这是代表已转换为IgG的局部黏膜反应,还是可能由归巢至结肠黏膜的外周抗原引发的外周反应。UC中分泌IgG的细胞和同种型转换变体的克隆分布尚不清楚。
研究UC中黏膜IgG的克隆分布,并在UC患者的正常和病变黏膜及血液中寻找相关的IgG和IgA分泌细胞。研究在正常黏膜和UC中可区分黏膜和外周库的特征。
对两名UC患者的血液、正常和病变黏膜进行了研究。
采用免疫球蛋白基因分析和克隆特异性聚合酶链反应研究UC患者黏膜和血液中IgG及相关IgA的克隆分布和特征。
UC患者黏膜中的IgG反应包括广泛的细胞克隆,这些克隆存在于病变黏膜和血液中,但在正常黏膜中很少见。检测到克隆相关的IgA类转换变体,均为IgA1,且也仅存在于病变黏膜和血液中。这表明这些克隆优先归巢至病变黏膜。我们发现JH1的使用是外周库的特征,并且在UC的黏膜IgG中观察到了JH1使用的实例。
总体而言,这些数据与UC的一种模型一致,即外周反应在结肠黏膜中表达并扩展。