A CD57+ CTL Degranulation Assay Effectively Identifies Familial Hemophagocytic Lymphohistiocytosis Type 3 Patients
A CD57+ CTL Degranulation Assay Effectively Identifies Familial Hemophagocytic Lymphohistiocytosis Type 3 Patients
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DOI：
10.1007/s10875-016-0357-3
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发表时间：
2017-01-01
影响因子：
9.1
通讯作者：
Heike, Toshio
中科院分区：
文献类型：
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作者：
Hori, Masayuki;Yasumi, Takahiro;Heike, Toshio
家族性噬血细胞淋巴组织细胞增生症3型(FHL3)是一种导致免疫失调的遗传性疾病。它需要及时和准确的诊断。自然杀伤(NK)细胞脱颗粒试验通常用于筛查FHL3患者。然而，我们最近遇到了两个携带新的UNC13D错义突变的晚发性FHL3病例：在这些病例中，使用新鲜分离的和白细胞介素2(IL)-2激活的NK细胞进行脱颗粒试验得出了相互矛盾的结果。由于CD57(+)细胞毒性T淋巴细胞(CTL)脱颗粒缺陷有助于FHL3的诊断，我们评估了CD57(+)CTL脱颗粒试验是否比NK细胞检测更有效地识别FHL3患者。通过检测NK细胞穿孔素表达和血小板Munc13-4、Synaxin-11和Munc18-2的表达，以及NK细胞和CTL脱颗粒检测，前瞻性筛查了40例FHL3患者。新分离的NK细胞脱颗粒试验对FHL3患者具有较高的敏感性(100%)和较低的特异性(71%)。IL-2刺激的NK细胞检测的特异性有所提高，但31例非FHL3患者中仍有3例脱颗粒低于阈值水平。CD57(+)CTL脱颗粒试验对FHL3的诊断具有较高的敏感性和特异性(均为100%)，CD57(+)CTL脱颗粒试验比基于NK细胞的检测更有效地诊断FHL3患者。
Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic disorder that results in immune dysregulation. It requires prompt and accurate diagnosis. A natural killer (NK) cell degranulation assay is often used to screen for FHL3 patients. However, we recently encountered two cases of late-onset FHL3 carrying novel UNC13D missense mutations: in these cases, the degranulation assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded contradictory results. Since the defective degranulation of CD57(+) cytotoxic T lymphocytes (CTLs) in these cases was helpful for making the diagnosis, we assessed whether the CD57(+) CTL degranulation assay more effectively identified FHL3 patients than the NK cell assays.Forty additional patients with hemophagocytic lymphohistiocytosis were prospectively screened for FHL3 by measuring the perforin expression in NK cells and the expression of Munc13-4, syntaxin-11, and Munc18-2 in platelets and by performing NK cell and CTL degranulation assays. The results were confirmed by genetic analysis.The freshly isolated NK cell degranulation assay detected FHL3 patients with high sensitivity (100%) but low specificity (71%). The IL-2-stimulated NK cell assay had improved specificity, but 3 out of the 31 non-FHL3 patients still showed degranulation below the threshold level. The CD57(+) CTL degranulation assay identified FHL3 patients with high sensitivity and specificity (both 100%).The CD57(+) CTL degranulation assay more effectively identified FHL3 patients than the NK cell-based assays.