Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-g) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

背景：CD64（FcγR1）是单体IgG1与IgG3的高亲和力受体。循环中性粒细胞在其细胞表面仅表达极微量的CD64。
研究目标：本研究的首要目的为探究中性粒细胞CD64表面表达作为活动性肺结核（TB）生物标志物的应用价值。我们提出假说：结核感染中升高的中性粒细胞CD64表达水平，与作为CD64表达诱导剂的干扰素γ（IFN-γ）存在相关性。
研究方法：作为巴西一项前瞻性队列研究的组成部分，本研究采用Leuko64试剂盒通过流式细胞术，定量检测了肺结核患者、潜伏性结核感染（LTBI）患者及健康对照者的样本中每个中性粒细胞的CD64表达水平（PMN CD64指数）。
研究结果：肺结核患者的PMN CD64指数显著高于健康对照者与潜伏性结核感染患者。受试者工作特征曲线分析显示，PMN CD64指数可有效区分肺结核患者与潜伏性结核感染患者及健康个体。经治疗后，患者的PMN CD64指数可恢复至基线水平。
研究结论：活动性肺结核患者循环中性粒细胞的CD64表达正向调控现象，可作为活动性肺结核诊断的补充生物标志物，同时可用于监测潜伏性结核感染患者向活动性肺结核疾病进展的过程。