A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes
A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes
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DOI：
10.1182/blood-2011-08-374199
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发表时间：
2012-03-22
期刊：
影响因子：
20.3
通讯作者：
Ehl, Stephan
中科院分区：
文献类型：
--
作者：
Bryceson, Yenan T.;Pende, Daniela;Ehl, Stephan
家族性噬血细胞性淋巴组织细胞增生症（FHL）是一种由淋巴细胞毒性缺陷引起的危及生命的免疫调节障碍。噬血细胞性淋巴组织细胞增生症（HLH）的原发性、遗传性形式与继发性形式的快速鉴别对于治疗决策至关重要。我们前瞻性地评估了一个494例疑似HLH患者队列中，基于自然杀伤（NK）细胞和细胞毒性T淋巴细胞表面CD 107 a上调的脱颗粒试验的性能。77例FHL 3 -5患者中的75例（97%）和13例Griscelli综合征2型或Chediak-Higashi综合征患者中的11例（85%）存在异常静息NK细胞脱颗粒。与此相反，NK细胞脱颗粒是正常的14/16例（88%）与X连锁淋巴组织增生性疾病和8/14例（57%）与FHL 2，谁被确定为减少细胞内SLAM相关蛋白（SAP），X连锁凋亡抑制蛋白（XIAP），穿孔素表达，分别。在66例临床诊断为继发性HLH的患者中，13/59例（22%）有异常静息NK细胞脱颗粒，而43例中0例有使用IL-2激活的NK细胞的异常脱颗粒。活动性疾病或免疫抑制治疗不会损害检测性能。总体而言，静息NK细胞脱粒低于5%提供了96%的敏感性遗传性脱粒疾病和88%的特异性。因此，脱颗粒测定允许对患者进行快速和可靠的分类，从而有利于治疗决策。（血。2012; 119（12）：2754-2763）
Familial hemophagocytic lymphohistiocytosis (FHL) is a life-threatening disorder of immune regulation caused by defects in lymphocyte cytotoxicity. Rapid differentiation of primary, genetic forms from secondary forms of hemophagocytic lymphohistiocytosis (HLH) is crucial for treatment decisions. We prospectively evaluated the performance of degranulation assays based on surface up-regulation of CD107a on natural killer (NK) cells and cytotoxic T lymphocytes in a cohort of 494 patients referred for evaluation for suspected HLH. Seventy-five of 77 patients (97%) with FHL3-5 and 11 of 13 patients (85%) with Griscelli syndrome type 2 or Chediak-Higashi syndrome had abnormal resting NK-cell degranulation. In contrast, NK-cell degranulation was normal in 14 of 16 patients (88%) with X-linked lymphoproliferative disease and in 8 of 14 patients (57%) with FHL2, who were identified by diminished intracellular SLAM-associated protein (SAP), X-linked inhibitor of apoptosis protein (XIAP), and perforin expression, respectively. Among 66 patients with a clinical diagnosis of secondary HLH, 13 of 59 (22%) had abnormal resting NK-cell degranulation, whereas 0 of 43 had abnormal degranulation using IL-2-activated NK cells. Active disease or immunosuppressive therapy did not impair the assay performance. Overall, resting NK-cell degranulation below 5% provided a 96% sensitivity for a genetic degranulation disorder and a specificity of 88%. Therefore, degranulation assays allow a rapid and reliable classification of patients, benefiting treatment decisions. (Blood. 2012; 119(12):2754-2763)