Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Frederick, Md.
Laboratory of Parasitic Diseases, Clinical Research Directorate/CMRP, SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, Frederick, Md.
J Allergy Clin Immunol. 2014 Apr;133(4):1195-202. doi: 10.1016/j.jaci.2013.06.037. Epub 2013 Aug 26.
Although most patients with hypereosinophilic syndromes (HES) present with clinical signs and symptoms attributable to eosinophilic tissue infiltration, some untreated patients remain asymptomatic or have signs and symptoms, such as allergic rhinitis, for which the relationship to peripheral eosinophilia is unclear (hypereosinophilia of unknown significance [HEUS]).
To identify and characterize subjects with HEUS of 5 years duration or more as compared to untreated patients with symptomatic HES and healthy normal volunteers.
All subjects with eosinophilia underwent yearly evaluation, including a standardized clinical evaluation, whole blood flow cytometry to assess lymphocyte subsets and eosinophil activation, and serum collection. Peripheral blood mononuclear cells were cultured overnight with and without phorbol 12-myristate 13-acetate/ionomycin. Cytokines and chemokines were measured in serum and cell supernatants, and mRNA expression was assessed by using quantitative real-time PCR.
Eight of the 210 subjects referred for the evaluation of eosinophilia (absolute eosinophil count [AEC] > 1500/μL) met the criteria for HEUS of 5 years duration or more (range, 7-29 years). Peak eosinophil count and surface expression of eosinophil activation markers were similar in subjects with HEUS and in untreated subjects with platelet-derived growth factor alpha-negative HES (n = 28). Aberrant or clonal T-cell populations were identified in 50% of the subjects with HEUS as compared to 29% of the subjects with HES (P = .12). Increased levels of IL-5, GM-CSF, IL-9, and IL-17A were also comparable in subjects with HEUS and HES. Serum levels of IgE and IL-13 were significantly increased only in subjects with HES.
A small number of patients with persistent peripheral eosinophilia (AEC > 1500/μL) appear to have clinically benign disease.
尽管大多数高嗜酸性粒细胞综合征（HES）患者表现出可归因于嗜酸性粒细胞组织浸润的临床体征和症状，但一些未经治疗的患者仍无症状或有体征和症状，如过敏性鼻炎，其与外周血嗜酸性粒细胞增多的关系尚不清楚（意义未明的高嗜酸性粒细胞增多症[HEUS]）。
与未经治疗的有症状 HES 患者和健康正常志愿者相比，确定并描述 HEUS 持续 5 年或以上的患者，并对其进行特征描述。
所有嗜酸性粒细胞增多症患者均接受每年评估，包括标准化临床评估、全血流式细胞术评估淋巴细胞亚群和嗜酸性粒细胞活化，以及血清采集。外周血单核细胞在有佛波醇 12-肉豆蔻酸 13-乙酸/离子霉素和无佛波醇 12-肉豆蔻酸 13-乙酸/离子霉素的情况下培养过夜。在血清和细胞上清液中测量细胞因子和趋化因子，并通过实时定量 PCR 评估 mRNA 表达。
210 例因嗜酸性粒细胞增多症（绝对嗜酸性粒细胞计数[AEC]＞1500/μL）就诊的患者中，有 8 例符合 HEUS 持续 5 年或以上的标准（范围为 7-29 年）。HEUS 患者和血小板衍生生长因子-α 阴性 HES 未治疗患者（n=28）的嗜酸性粒细胞计数峰值和表面表达的嗜酸性粒细胞活化标志物相似。与 HES 患者的 29%相比，HEUS 患者中 50%存在异常或克隆性 T 细胞群（P=0.12）。HEUS 患者和 HES 患者的 IL-5、GM-CSF、IL-9 和 IL-17A 水平也相当。仅在 HES 患者中，血清 IgE 和 IL-13 水平显著升高。
少数持续性外周血嗜酸性粒细胞增多（AEC＞1500/μL）的患者似乎患有临床良性疾病。
