WHIM 综合征：从发病机制到个体化医学和治疗。
WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.
机构信息
Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 44195, USA.
出版信息
J Clin Immunol. 2019 Aug;39(6):532-556. doi: 10.1007/s10875-019-00665-w. Epub 2019 Jul 16.
WHIM syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow; monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. WHIM syndrome is usually caused by autosomal dominant mutations in the G protein-coupled chemokine receptor CXCR4 that impair desensitization, resulting in enhanced and prolonged G protein- and β-arrestin-dependent responses. Accordingly, CXCR4 antagonists have shown promise as mechanism-based treatments in phase 1 clinical trials. This review is based on analysis of all 105 published cases of WHIM syndrome and covers current concepts, recent advances, unresolved enigmas and controversies, and promising future research directions.
WHIM 综合征是一种罕见的联合性原发性免疫缺陷病，其名称由诊断四联征（疣、低丙种球蛋白血症、感染和骨髓细胞滞留）的首字母缩略词组成。骨髓细胞滞留是一种独特的非周期性严重先天性中性粒细胞减少症，由成熟和退化的中性粒细胞在骨髓中积累引起；单核细胞减少症和淋巴细胞减少症，特别是 B 淋巴细胞减少症，也很常见。WHIM 综合征通常由 G 蛋白偶联趋化因子受体 CXCR4 的常染色体显性突变引起，该突变损害脱敏作用，导致增强和延长 G 蛋白和β-arrestin 依赖性反应。因此，CXCR4 拮抗剂已在 1 期临床试验中作为基于机制的治疗方法显示出前景。本综述基于对所有 105 例 WHIM 综合征发表病例的分析，涵盖了当前的概念、最新进展、未解决的谜团和争议，以及有前途的未来研究方向。
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