Yang Yuanyuan, Tu Songtao, Peng Hongwei, Lu Jialiang, Yu Hua, Zhou Yulan, Dong Xiaowu, Li Fei
Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Clin Rev Allergy Immunol. 2025 Jun 9;68(1):56. doi: 10.1007/s12016-025-09068-9.
Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening hyperinflammatory disorder characterized by dysregulated immune activation, primarily driven by excessive stimulation of cytotoxic lymphocytes (CTLs) and macrophages. This uncontrolled immune response leads to cytokine-induced tissue damage and multiorgan dysfunction. HLH presents a significant clinical challenge due to its rapid progression and high mortality rate. In adult patients, current first-line treatment strategies, adapted from pediatric protocols such as HLH-94 and HLH-2004, achieve complete disease resolution in only approximately 50% of cases. The urgent need for more effective therapeutic options is underscored by the lack of targeted treatments and the persistent high mortality associated with HLH. However, the pathophysiology of HLH remains complex and incompletely understood, involving multiple immune dysregulations, diverse etiologies, and variable clinical presentations, making drug development particularly challenging. Drawing from recent advancements, this review provides a translational perspective on the immunopathological mechanisms underlying HLH, highlighting emerging therapeutic targets and novel treatments currently under clinical investigation. By synthesizing these insights, we aim to identify key opportunities for the development of innovative therapies to improve patient outcomes.
噬血细胞性淋巴组织细胞增生症（HLH）是一种严重且危及生命的高炎症性疾病，其特征为免疫激活失调，主要由细胞毒性淋巴细胞（CTLs）和巨噬细胞的过度刺激驱动。这种不受控制的免疫反应会导致细胞因子诱导的组织损伤和多器官功能障碍。由于HLH进展迅速且死亡率高，它带来了重大的临床挑战。在成年患者中，目前借鉴HLH - 94和HLH - 2004等儿科方案的一线治疗策略仅在约50%的病例中实现了疾病的完全缓解。缺乏靶向治疗以及与HLH相关的持续高死亡率凸显了对更有效治疗方案的迫切需求。然而，HLH的病理生理学仍然复杂且尚未完全理解，涉及多种免疫失调、不同病因和多变的临床表现，这使得药物开发极具挑战性。借鉴近期的进展，本综述提供了关于HLH潜在免疫病理机制的转化视角，突出了正在进行临床研究的新兴治疗靶点和新疗法。通过综合这些见解，我们旨在确定开发创新疗法以改善患者预后的关键机会。
