Department of Hematology, Radboud University Nijmegen Medical Center, HB Nijmegen, The Netherlands.
Clin Immunol. 2010 Aug;136(2):302-6. doi: 10.1016/j.clim.2010.04.007. Epub 2010 May 10.
Dectin-1 plays an important role in antifungal immunity. The dectin-1 Y238X polymorphism, which results in decreased Th17 responses, is associated with increased Candida colonization of stem cell transplantation (SCT) recipients. In this study we found no impact of the polymorphism on the incidence of graft-versus-host disease (GvHD), or on disease-free and overall survival in these SCT recipients. However, patients from patient-donor pairs bearing the wild-type allele who where colonized with Candida had a significant increased incidence of acute GvHD compared to non-colonized patients (OR=2.6, P=0.04). The fact that this was not the case in patients from pairs with the Y238X polymorphism (OR=1.2, ns) suggests that despite increased colonization defective dectin-1 signaling might have prevented an impact of Candida colonization on the incidence of acute GvHD to occur. These are the first human data showing a role for Candida in the pathogenesis of acute GvHD. The mechanism could involve C-type lectin receptor mediated Th17 responses.
Dectin-1 在抗真菌免疫中发挥重要作用。导致 Th17 反应减弱的 dectin-1 Y238X 多态性与干细胞移植 (SCT) 受者中念珠菌定植增加有关。在这项研究中，我们没有发现该多态性对 GvHD 的发生率或这些 SCT 受者的无病生存和总生存有影响。然而，在携带野生型等位基因且被念珠菌定植的患者与未定植的患者相比，急性 GvHD 的发生率显著增加 (OR=2.6，P=0.04)。在具有 Y238X 多态性的患者中并非如此 (OR=1.2，无统计学意义)，这表明尽管定植缺陷的 dectin-1 信号传导增加，但念珠菌定植对急性 GvHD 发生率的影响可能得以预防。这些是首次表明念珠菌在急性 GvHD 发病机制中起作用的人类数据。其机制可能涉及 C 型凝集素受体介导的 Th17 反应。
