Di Sabatino A, D'Alò S, Millimaggi D, Ciccocioppo R, Parroni R, Sciarra G, Cifone M G, Corazza G R
Gastroenterology Unit, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy.
Immunology. 2001 Aug;103(4):435-40. doi: 10.1046/j.1365-2567.2001.01245.x.
In coeliac disease (CD) immunological abnormalities are not confined to the small bowel and it has been suggested that changes in peripheral blood lymphocytes (PBL), such as lymphopenia and increased T-cell activation, may predispose to malignant or autoimmune complications of this condition. In the light of the recent findings about the Fas-Fas ligand (FasL) system in regulating lymphocyte homeostasis, the aim of the present study was to investigate peripheral lymphocyte Fas-mediated apoptosis in CD to establish whether the homeostatic role of apoptosis in peripheral T-cell selection is maintained. Moreover, because a soluble form of Fas has been described to be functionally implicated in the Fas signalling system, suggesting a relationship between some disorders and soluble Fas function, we measured levels of soluble Fas in sera of coeliac patients and analysed the relationship between these levels and the proportions of apoptotic and Fas(+) PBL to further explore the function of the Fas-FasL pathway in this condition. Finally, we evaluated whether the increased prevalence of anticardiolipin antibodies, recently described in CD, could be related to PBL apoptosis in this condition. We demonstrated an increased apoptosis and higher levels of Fas and FasL expression in PBL isolated from untreated coeliac patients when compared to treated coeliac patients and controls. In addition, low levels of soluble Fas and a significant positive correlation between anticardiolipin antibodies and PBL apoptosis were found in untreated CD. Then, our results showed an increased susceptibility of PBL to undergo Fas-mediated apoptosis in active CD. This increased apoptosis could be responsible for both lymphopenia and immunogenic exposure of phospholipids with subsequent production of autoantibodies.
在乳糜泻（CD）中，免疫异常并不局限于小肠，有人提出外周血淋巴细胞（PBL）的变化，如淋巴细胞减少和T细胞活化增加，可能易导致该疾病的恶性或自身免疫并发症。鉴于最近关于Fas-Fas配体（FasL）系统在调节淋巴细胞稳态方面的发现，本研究的目的是调查CD患者外周淋巴细胞Fas介导的凋亡，以确定凋亡在外周T细胞选择中的稳态作用是否得以维持。此外，由于已描述可溶性Fas在Fas信号系统中具有功能作用，提示某些疾病与可溶性Fas功能之间存在关联，我们检测了乳糜泻患者血清中可溶性Fas的水平，并分析了这些水平与凋亡性和Fas(+) PBL比例之间的关系，以进一步探索Fas-FasL途径在这种情况下的功能。最后，我们评估了最近在CD中描述的抗心磷脂抗体患病率增加是否可能与这种情况下的PBL凋亡有关。我们证明，与接受治疗的乳糜泻患者和对照组相比，从未经治疗的乳糜泻患者分离出的PBL中凋亡增加，Fas和FasL表达水平更高。此外，在未经治疗的CD中发现可溶性Fas水平较低，抗心磷脂抗体与PBL凋亡之间存在显著正相关。然后，我们的结果表明，在活动性CD中PBL对Fas介导的凋亡更敏感。这种凋亡增加可能是淋巴细胞减少和磷脂免疫原性暴露继而产生自身抗体的原因。
