Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members
Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members
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DOI：
10.1182/blood.v99.1.61
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发表时间：
2002-01-01
期刊：
影响因子：
20.3
通讯作者：
Filipovich, AH
中科院分区：
文献类型：
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作者：
Kogawa, K;Lee, SM;Filipovich, AH
穿孔素基因突变在一些噬血细胞淋巴组织细胞增生症(HLH)患者中已被描述，但穿孔素缺陷在HLH发病机制中的作用尚不清楚。用四色流式细胞术建立各年龄段正常人穿孔素的正常表达模式，并对HLH患者及其家属的细胞毒性淋巴细胞(自然杀伤细胞、CD8(+)T细胞、CD56(+)T细胞)的穿孔素染色模式进行研究。前瞻性分析11例无血缘关系的HLH患者和19例家系成员。7例原发HLH患者中有4例在所有细胞毒细胞类型中均缺乏细胞内穿孔素。4例患者均表现出穿孔素基因突变。他们的父母是穿孔素突变的专性携带者，有异常的穿孔素染色模式。对来自其他3名原发HLH患者和其余家庭成员的细胞毒细胞的分析表明，穿孔素阳性的细胞毒细胞比例正常。另一方面，4例Epstein-Barr病毒相关性HLH患者的NK细胞数量明显减少，但CD8(+)T细胞比例显著增加，穿孔素表达。四色流式细胞术提供的诊断信息与墨水功能降低的证据相结合，可能会加速某些家族中威胁生命的HLH的识别，并指导对该综合征的进一步遗传学研究。
Mutations in the perforin gene have been described in some patients with hemophagocytic lymphohistiocytosis (HLH), but the role of perforin defects in the pathogenesis of HLH remains unclear. Four-color flow cytometric analysis was used to establish normal patterns of perforin expression for control subjects of all ages, and patterns of perforin staining in cytotoxic lymphocytes (natural killer [NK] cells, CD8(+) T cells, CD56(+) T cells) from patients with HLH and their family members were studied. Eleven unrelated HLH patients and 19 family members were analyzed prospectively. Four of the 7 patients with primary HLH showed lack of intracellular perforin in all cytotoxic cell types. All 4 patients showed mutations in the perforin gene. Their parents, obligate carriers of perforin mutations, had abnormal perforin-staining patterns. Analysis of cytotoxic cells from the other 3 patients with primary HLH and remaining family members had normal percentages of perforin-positive cytotoxic cells. On the other hand, the 4 patients with Epstein-Barr virus-associated HLH typically had depressed numbers of NK cells but markedly increased proportions of CD8(+) T cells with perforin expression. Four-color flow cytometry provides diagnostic information that, in conjunction with evidence of reduced INK function, may speed the identification of life-threatening HLH in some families and direct further genetic studies of the syndrome.