D'Haens G, Hiele M, Rutgeerts P, Geboes K, Ceuppens J L
Department of Internal Medicine, Leuven University Hospital, Belgium.
Gut. 1994 Dec;35(12):1728-33. doi: 10.1136/gut.35.12.1728.
Earlier studies regarding possible primary immune disturbances participating in the pathogenesis of Crohn's disease yielded conflicting results. Peripheral blood lymphocyte subsets and lymphocyte proliferative responses to five soluble recall antigens and to the polyclonal stimulator phythaemagglutinin were therefore measured in 17 patients with active Crohn's disease, before and six months after surgical resection of the inflamed intestine and in 16 healthy controls. Lymphocyte proliferation in response to all five recall antigens was significantly lower in patients than in controls. No significant differences with controls were detected after surgery. Addition of indomethacin to phythaemagglutinin stimulated lymphocyte cultures had a stronger proliferation enhancing effect in patients than in controls, resulting in comparable proliferative responses in both groups. When both indomethacin and prostaglandin E2 were added, inhibition of reactivity by prostaglandin E2 was stronger in patients' cultures. This suggests a higher sensitivity to inflammatory prostaglandins in Crohn's disease. The degree of lymphocyte stimulation by antigens correlated positively with the percentage of circulating memory T cells (CD 45 RA-). The percentage of activated (HLA-DR+) CD8 cells was higher in patients than in controls. The CD4/CD8 ratio, which was not significantly different between patients and controls, correlated significantly with disease activity and characteristics, even in the postoperative phase. These findings suggest that immune abnormalities in Crohn's disease fluctuate with and are probably secondary to inflammatory activity.
早期关于可能参与克罗恩病发病机制的原发性免疫紊乱的研究结果相互矛盾。因此,对17例活动期克罗恩病患者、16例健康对照者进行了研究,检测了他们外周血淋巴细胞亚群以及淋巴细胞对五种可溶性回忆抗原和多克隆刺激剂植物血凝素的增殖反应。这些患者在发炎肠道手术切除前和切除后6个月均接受了检测。患者对所有五种回忆抗原的淋巴细胞增殖反应均显著低于对照组。术后与对照组未检测到显著差异。在植物血凝素刺激的淋巴细胞培养物中添加吲哚美辛后,患者组的增殖增强作用比对照组更强,导致两组的增殖反应相当。当同时添加吲哚美辛和前列腺素E2时,前列腺素E2对患者培养物反应性的抑制作用更强。这表明克罗恩病患者对炎性前列腺素更为敏感。抗原刺激淋巴细胞的程度与循环记忆T细胞(CD45 RA-)的百分比呈正相关。患者活化(HLA-DR+)CD8细胞的百分比高于对照组。患者与对照组之间的CD4/CD8比值无显著差异,但即使在术后阶段,该比值也与疾病活动度和特征显著相关。这些发现表明,克罗恩病中的免疫异常随炎症活动而波动,且可能是炎症活动的继发结果。