The WHIM syndrome features susceptibility to human Papillomavirus infection-induced warts and carcinomas, hypogammaglobulinemia, recurrent bacterial infections, B and T-cell lymphopenia, and neutropenia associated with retention of senescent neutrophils in the bone marrow (i.e. myelokathexis). This rare disorder is mostly linked to inherited heterozygous autosomal dominant mutations in the gene encoding CXCR4, a G protein coupled receptor with a unique ligand, the chemokine CXCL12/SDF-1. Some individuals who have full clinical forms of the syndrome carry a wild type CXCR4 gene. In spite of this genetic heterogeneity, leukocytes from WHIM patients share in common dysfunctions of the CXCR4-mediated signaling pathway upon exposure to CXCL12. Dysfunctions are characterized by impaired desensitization and receptor internalization, which are associated with enhanced responses to the chemokine. Our increasing understanding of the mechanisms that account for the aberrant CXCL12/CXCR4-mediated responses is beginning to provide insight into the pathogenesis of the disorder. As a result we can expect to identify markers of the WHIM syndrome, as well as other disorders with WHIM-like features that are associated with dysfunctions of the CXCL12/CXCR4 axis.

中文翻译：

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CXCL12/CXCR4 轴功能障碍：罕见免疫缺陷疾病 WHIM 综合征的标志。

WHIM 综合征的特点是对人乳头瘤病毒感染引起的疣和癌、低丙种球蛋白血症、复发性细菌感染、B 和 T 细胞淋巴细胞减少以及与衰老中性粒细胞在骨髓中滞留相关的中性粒细胞减少症（即骨髓衰竭）的易感性。这种罕见的疾病主要与编码CXCR4的基因中的遗传性杂合常染色体显性突变有关，CXCR4是一种 G 蛋白偶联受体，具有独特的配体趋化因子 CXCL12/SDF-1。一些具有完整临床形式的综合征的个体携带野生型CXCR4基因。尽管存在这种遗传异质性，但 WHIM 患者的白细胞在暴露于 CXCL12 时存在 CXCR4 介导的信号通路的常见功能障碍。功能障碍的特征是脱敏和受体内化受损，这与对趋化因子的反应增强有关。我们对 CXCL12/CXCR4 介导的异常反应机制的日益了解开始提供对该疾病发病机制的深入了解。因此，我们可以期望识别 WHIM 综合征的标志物，以及其他具有 WHIM 样特征的疾病，这些特征与 CXCL12/CXCR4 轴功能障碍相关。