Anderson Charles F, Makiya Michelle, Xiong Knaunong, Penrod Lori, Wetzler Lauren, Ware JeanAnne, Constantine Gregory M, Khoury Paneez, Klion Amy D
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
J Allergy Clin Immunol. 2025 May 9. doi: 10.1016/j.jaci.2025.04.027.
Lymphocytic variant hypereosinophilic syndrome (LHES) is a rare disorder characterized by hypereosinophilia, the presence of phenotypically aberrant populations of T2 lymphocytes, and varied clinical manifestations. Although disease pathogenesis has historically been attributed to IL-5-driven hypereosinophilia, response to eosinophil-lowering biologics is not universal, suggesting a more direct role for the aberrant lymphocyte population in disease pathogenesis.
We sought to further delineate the surface phenotypes and cytokine profiles of the aberrant lymphocyte populations in patients with LHES.
Multiparameter flow cytometry was used to analyze lymphocytes in whole blood and stored peripheral blood mononuclear cells from a cohort of 42 untreated and treated patients with LHES.
Surface receptor profiling of the aberrant population in 22 untreated patients with LHES, including 8 patients with episodic angioedema with eosinophilia, confirmed prior data demonstrating that the aberrant CD4 T-cell populations in LHES have a T2 memory phenotype. CCR8 was identified as a dominant surface marker, unaffected by sample processing or patient treatment status. Serum levels of CCL1, the ligand for CCR8, were increased in LHES patients compared to patients with other hypereosinophilic syndrome subtypes. Expanded populations of FoxP3HeliosCCR8 regulatory T cells were identified in many patients with CD3CD4 LHES and correlated with the size of the CD3CD4 population.
These data provide further evidence for direct involvement of the aberrant T-cell populations in disease pathogenesis in LHES and a rationale for further exploration of T-cell-directed therapies.
淋巴细胞变异型嗜酸性粒细胞增多综合征（LHES）是一种罕见疾病，其特征为嗜酸性粒细胞增多、存在表型异常的T2淋巴细胞群以及多样的临床表现。尽管疾病发病机制在历史上一直归因于白细胞介素-5驱动的嗜酸性粒细胞增多，但对降低嗜酸性粒细胞的生物制剂的反应并不普遍，这表明异常淋巴细胞群在疾病发病机制中发挥了更直接的作用。
我们试图进一步描绘LHES患者异常淋巴细胞群的表面表型和细胞因子谱。
采用多参数流式细胞术分析42例未经治疗和已治疗的LHES患者全血及储存的外周血单核细胞中的淋巴细胞。
对22例未经治疗的LHES患者（包括8例伴有嗜酸性粒细胞增多的发作性血管性水肿患者）的异常细胞群进行表面受体分析，证实了先前的数据，即LHES中异常的CD4 T细胞群具有T2记忆表型。CCR8被确定为主要表面标志物，不受样本处理或患者治疗状态的影响。与其他嗜酸性粒细胞增多综合征亚型的患者相比，LHES患者血清中CCR8配体CCL1的水平升高。在许多CD3CD4 LHES患者中发现了FoxP3HeliosCCR8调节性T细胞的扩增群，且与CD3CD4群的大小相关。
这些数据为异常T细胞群直接参与LHES疾病发病机制提供了进一步证据，并为进一步探索T细胞导向疗法提供了理论依据。
