Sadeghi Mahmoud, Lahdou Imad, Opelz Gerhard, Mehrabi Arianeb, Zeier Martin, Schnitzler Paul, Daniel Volker
Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany.
Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
BMC Immunol. 2016 Oct 3;17(1):35. doi: 10.1186/s12865-016-0175-7.
Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation.
IL-21 plasma levels were similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV-seronegative (p = 0.002) and -seropositive (p < 0.001) patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation (p = 0.025).
Our results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory mediator of latent CMV infection in patients with ESRD and predisposes patients for post-transplant CMV reactivation.
巨细胞病毒血清阳性是终末期肾病(ESRD)患者动脉粥样硬化的独立危险因素。供体巨细胞病毒血清阳性与更高的移植物丢失相关。树突状细胞、巨噬细胞和Th17淋巴细胞被定义为白细胞介素-23(IL-23)的产生者。IL-23被认为参与促进Th17细胞极化。潜伏性巨细胞病毒诱导的Th17可能参与ESRD患者巨细胞病毒感染的发病机制。我们旨在评估Th17依赖性细胞因子与ESRD、巨细胞病毒状态及肾移植术后结局之间的关联。
患者和健康对照者的血浆IL-21水平相似(p = 0.47),而ESRD患者的IL-9(p = 0.02)和IL-23(p < 0.0001)水平显著更高。巨细胞病毒血清阴性(p = 0.002)和血清阳性(p < 0.001)患者的血浆IL-23水平显著高于对照者。巨细胞病毒血清阳性患者的血浆IL-23水平显著高于巨细胞病毒血清阴性患者(p < 0.001)。移植后发生巨细胞病毒再激活的患者的血浆IL-23水平高于未发生巨细胞病毒再激活的患者(p = 0.025)。
我们的结果表明潜伏性巨细胞病毒诱导IL-23。IL-23可能是ESRD患者潜伏性巨细胞病毒感染的炎症介质,并使患者易发生移植后巨细胞病毒再激活。