Erdheim-Chester disease (ECD) is a rare, systemic, non-Langerhans cell histiocytosis neoplasm, which is characterized by the infiltration of CD63+ CD1a- histiocytes in multiple tissues. The BRAFV600E mutation is frequently present in individuals with ECD and has been detected in hematopoietic stem cells and immune cells from the myeloid and systemic compartments. Immune cells and proinflammatory cytokines are present in lesions, suggesting ECD involves immune cell recruitment. Although a systemic cytokine Th-1-oriented signature has been reported in ECD, the immune cell network orchestrating the immune response in ECD has yet to be described. To address this question, the phenotypes of circulating leukocytes were investigated in a large, single-center cohort of 78 patients with ECD and compared with a group of 21 control individuals. Major perturbations in the abundance of systemic immune cells were detected in patients with ECD, with a decrease in circulating plasmacytoid, myeloid 1, and myeloid 2 dendritic cells, mostly in BRAFV600E carriers, in comparison with individuals in the control group. Similarly, a marked decrease in blood T-helper, cytotoxic, and B lymphocyte numbers was observed in patients with ECD, relative to the control group. Measurement of circulating immunoglobulin concentrations revealed an immunoglobulin G switch, from IgG1 to IgG4 subclasses, which are more frequently associated with the BRAF mutation. First-line therapies, including pegylated IFNlland vemurafenib, were able to correct most of these alterations. This study reports a profound disturbance in the systemic immune phenotype in patients with ECD, providing important new information and helping to understand the physiopathological mechanisms involved in this rare disease and in the therapeutic management of patients.

中文翻译：

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在 78 名患者的单中心研究中，Erdheim-Chester 病的免疫表型和免疫球蛋白转换发生了深刻的系统性改变。

Erdheim-Chester 病 (ECD) 是一种罕见的全身性非朗格汉斯细胞组织细胞增生症肿瘤，其特征是 CD63+ CD1a- 组织细胞在多个组织中浸润。BRAFV600E 突变经常存在于 ECD 患者中，并且已在骨髓和全身隔室的造血干细胞和免疫细胞中检测到。免疫细胞和促炎细胞因子存在于病变中，表明 ECD 涉及免疫细胞募集。尽管已在 ECD 中报道了面向全身细胞因子 Th-1 的特征，但尚未描述在 ECD 中协调免疫反应的免疫细胞网络。为了解决这个问题，在一个包含 78 名 ECD 患者的大型单中心队列中研究了循环白细胞的表型，并与一组 21 名对照个体进行了比较。在 ECD 患者中检测到全身免疫细胞丰度的主要扰动，与对照组的个体相比，循环浆细胞样、髓样 1 和髓样 2 的树突状细胞减少，主要是 BRAFV600E 携带者。同样，相对于对照组，在 ECD 患者中观察到血液 T 辅助细胞、细胞毒性细胞和 B 淋巴细胞数量显着减少。循环免疫球蛋白浓度的测量显示免疫球蛋白 G 转换，从 IgG1 到 IgG4 亚类，这更常与 BRAF 突变相关。包括聚乙二醇化 IFNll 和威罗非尼在内的一线疗法能够纠正这些改变中的大部分。这项研究报告了 ECD 患者全身免疫表型的严重紊乱，