慢性移植物抗宿主病的发病机制及治疗进展

Advances in pathogenesis and treatment of chronic graft resistance to persistent diseases

慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)是异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后患者晚期非复发相关死亡的重要原因,且严重影响患者的生活质量。cGVHD可累及全身多个系统,临床表现类似自身免疫性疾病,具有多样性,其主要病理表现为纤维化。以糖皮质激素为基础的治疗方案目前仍然是cGVHD的临床一线标准治疗措施,但由于长期大剂量激素的应用容易导致严重并发症,再加上糖皮质激素耐药和复发难治的cGVHD,传统的免疫抑制剂治疗对cGVHD的临床疗效有限。随着对cGVHD发病机制的深入了解,相关疗法如去除同种异体效应T细胞、去除B细胞、阻止B细胞的分化、靶向B细胞受体信号通路、抑制细胞因子受体介导的信号转导、Tregs体内扩增、Tregs过继性转移、促进Tregs重建预防cGVHD、抗纤维化治疗得到了临床和临床前试验结果的支持。

Chronic graft-versus-host disease(cGVHD)is a major cause for late non-relapse-related death in patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT),and seriously affects their quality of life.cGVHD may involve many systems in the whole body and its clinical manifestations are similar to autoimmune diseases,and the main pathology is fibrosis.The therapeutic regimen based on glucocorticoids remains as the first-line treatment for cGVHD.Since long-term and high-dose application of glucocorticoids result in serious complications,along with the appearance of steroid-resistant and recurrence/refractory cGVHD,conventionalimmune suppressive agents have limited clinical efficacy.With the progress in understanding of the pathological mechanisms for cGVHD,many treatments,such as depletion of alloreactive T cells,B-cell depletion,preventing B cell differentiation,targeting the B-cell receptor signaling pathway,inhibition of cytokine receptor–mediated signaling,enhancement of Tregs in vivo,adoptive Tregs therapy,facilitating Tregs reconstitution,and anti-fibrosis therapy,have been supported by clinical and preclinical results.