title: ITK Gene Mutation: Effect on Survival of Children with Severe Hemophagocytic Lymphohistiocytosis.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is characterized by deadly hyperinflammatory syndrome, but data on severe HLH with multi-organ dysfunction in children are scant. The authors report a retrospective study of 8 cases with severe HLH from a pediatric intensive care unit (PICU) over a 1-y period and found that Epstein barr virus (EBV) -infection was the most common etiology. All patients had genetic analysis, which showed that four patients with EBV -infection had one homozygous mutation, c.985+75G>A (at position chr5:156667232) in exon10 of the ITK gene with poor survival rates. ITK+mutation group had higher percentages of CD3+CD8+T cells (36.0 ± 8.4 %) than those in ITK-mutation group (28.8 ± 5.5 %), while they had similar levels of CD3+CD4+T cells. ITK+mutation group had lower proportion of CD3-CD19+B cells (16.3 ± 2.9 %) and CD16+CD56+NK cells (8.4 ± 2.6 %) than ITK-mutation group (29.6 ± 5.1 % and 15.9 ± 9.0 % respectively). Most importantly, patients with EBV infection with c.985+75G>A mutation in ITK had lower survival rates than ITK-mutation group which it may be related with cellular immune dysfunction.
authors.affiliation: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. fangzheng99@sina.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zha
authors.affiliation: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fangjun
authors.initials: F
authors.lastname: Cheng
mesh_terms: D002648:Child; D020031:Epstein-Barr Virus Infections; D005260:Female; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics*; D008297:Male; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase
keywords: Epstein-Barr virus; Gene mutation; Hemophagocytic lymphohistiocytosis; ITK; Multi-organ dysfunction