Objective: To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH).
Methods: Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations.
Results: The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a).
Conclusion: Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.
目的: 探讨家系基因筛查及快速免疫学指标检测在原发性噬血细胞综合征（HLH）诊断中的意义。
方法: 通过对伴有PRF1、UNC13D及SH2D1A基因突变的4例原发性HLH患者展开家系调查，分别完成基因筛查及各项免疫学指标检测（包括NK细胞活性、CD107a检测及HLH相关缺陷蛋白表达测定），评价各项检测指标在原发性HLH诊断中的意义并探讨各项指标间的相关性。
结果: 4个家系基因突变分别为PRF1基因错义突变c.T172C（p.S58P）和非框架移码突变c.1083_1094del (p.361_365del）；PRF1基因错义突变c.C1349T（p.T450M）和框架移码突变c.1090_1091delCT (p.T364fsX93）；UNC13D基因错义突变c.G2588A（p.G863D）；SH2D1A基因半合子错义突变c.32T>G (p.I11S）。先证者及家系成员分别存在不同程度的NK细胞活性降低，其中PRF1基因及SH2D1A基因突变家系HLH相关基因编码穿孔素蛋白、信号淋巴细胞活化分子相关蛋白（SAP）表达水平下降，UNC13D基因突变先证者及与其存在完全相同突变位点的家系成员细胞毒脱颗粒功能（CD107a表达）显著减低。
结论: 开展家系基因筛查及快速免疫学指标检测对诊断原发性HLH具有重要意义，两者具有较好的一致性，其中快速免疫学指标检测作为一种高效的检测手段，可为原发性HLH的早期诊断提供可靠依据。