Popko K, Jasińska J, Górska E, Demkow U, Balwierz W, Maciejka-Kembłowska L, Badowska W, Wachowiak J, Drabko K, Malinowska I
Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland.
Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
Adv Exp Med Biol. 2016;912:21-31. doi: 10.1007/5584_2016_210.
Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like autoimmune disorders, rheumatoid disorders, cancers, or infections. In the Polish population, FHLH is rather rare. The aim of the present study was to assess the immune function in a group of children with clinical symptoms suggesting FHLH. Forty five children with suspected HLH of the median age of 4 years and 15 healthy children, taken as a control group, were enrolled into the study. All presented results were obtained with the use of flow cytometry. In the HLH group, there were only three cases identified with the UNC13D gene mutation responsible for the FHLH3 phenotype. Another four children, without known mutation, were classified as FHLH because of frequent recurrence of the disease. In all cases of FHLH, cell cytotoxicity was impaired compared with healthy children (p = 0.003). Perforin expression in FHLH was normal or higher than that observed in controls (p = 0.09). In case of patients with mutation in the Munc13 protein, degranulation was lower than that in healthy children (<5 %). The findings of this study demonstrate that children with known mutations responsible for the FHLH development are immunocompromised. However, it requires further elucidation whether the presence of currently unknown mutations could lead to a similar phenotype.
噬血细胞性淋巴组织细胞增生症（HLH）是一种严重的全身综合征，与巨噬细胞过度活化及免疫系统调节受损有关。目前已认识到HLH有两种形式：基因决定型或家族型（FHLH），以及在原发性疾病（如自身免疫性疾病、类风湿性疾病、癌症或感染）过程中继发产生的类型。在波兰人群中，FHLH较为罕见。本研究的目的是评估一组有提示FHLH临床症状的儿童的免疫功能。45名疑似HLH的儿童（中位年龄4岁）和15名健康儿童作为对照组纳入研究。所有呈现的结果均通过流式细胞术获得。在HLH组中，仅发现3例由UNC13D基因突变导致FHLH3表型。另外4名无已知突变的儿童因疾病频繁复发被归类为FHLH。在所有FHLH病例中，与健康儿童相比，细胞毒性受损（p = 0.003）。FHLH中穿孔素表达正常或高于对照组（p = 0.09）。在Munc13蛋白有突变的患者中，脱颗粒低于健康儿童（<5%）。本研究结果表明，有导致FHLH发生的已知突变的儿童存在免疫功能低下。然而，目前未知的突变是否会导致类似的表型仍需进一步阐明。
