CD40L在川崎病发病机制中的作用探讨

The roles of CD40 ligand in the pathogenesis of Kawasaki disease

为探讨CD40L在儿童川崎病发病机制中的作用,用流式细胞技术及ELISA法检测急性期川崎病(KD)患儿外周血单个核细胞(PBMC)体外表达CD40L水平、细胞凋亡率及可溶性CD40L(sCD40L)对单核细胞株THP-1产生TNF-α的影响。结果:KD表达CD40L明显增高;存在淋巴细胞凋亡延迟;患儿PBMC培养上清(可能含有sCD40L)可诱导THP-1产生高浓度的TNF-α。抗CD40L单抗可纠正上述异常效应。CD40L的异常表达在川崎病的发病中起重要作用,抗CD40L单抗对KD 具有潜在的免疫学治疗前景。

To explore the roles of CD40 ligand (CD40L) in the pathogenesis of Kawasaki disease (KD) in children, CD40L expression and apoptosis cell count from peripheral blood mononuclear cells (PBMC) and tumor necrotic factor-α (TNF-α) from monocytes (THP-1) lines were detected by flow cytometry and ELISA in 22 children with KD and 23 normal children, respectively. The results showed that delayed apoptosis and increased expression of CD40L in PBMC were observed in children with KD comparing to normal children. The delayed apoptosis could be corrected when anti-CD40L mAb was added to the PBMC culture system. It was noticed that higher levels of TNF-a could be produced in the THP-1 lines that could be induced by sCD40L in the supernatants of PBMC culture system. Anti-CD40L mAb could also block the abnormal reaction of THP-1 lines. It is concluded that higher levels of CD40L expression may probably play a very important role in the pathogenesis of KD, it is possible that immunotherapy of anti-CD40L mAb will be available for the treatment of KD in the future.