A genetic analysis of children with Epstein-Barr virus-positive hemophagocytic lymphohistiocytosis and its association with T-helper type 1/T-helper type 2 cytokines.
- Author:
Yao ZHANG
1
;
Yong-Min TANG
Author Information
1. Pediatric Hematology and Oncology Center, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310003, China. y_m_tang@zju.edu.cn.
- Publication Type:Journal Article
- MeSH:
Child;
Cytokines;
Epstein-Barr Virus Infections;
complications;
Genetic Testing;
Herpesvirus 4, Human;
Humans;
Lymphohistiocytosis, Hemophagocytic;
genetics;
Membrane Proteins;
Th1 Cells;
Th2 Cells
- From:
Chinese Journal of Contemporary Pediatrics
2020;22(6):620-625
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effect of genetic variation on the prognosis of children with Epstein-Barr virus (EBV)-positive hemophagocytic lymphohistiocytosis (HLH) and its association with cytokines.
METHODS:A total of 81 EBV-positive HLH children who received the sequencing of related genes were enrolled. According to the results of gene detection, they were divided into a non-mutation group and a mutation group. According to the pattern of gene mutation, the mutation group was further divided into three subgroups: single heterozygous mutation (SHM), double heterozygous mutation (DHM), and homozygous or compound heterozygous mutation (H-CHM). The serum levels of cytokines were measured and their association with HLH gene mutations was analyzed.
RESULTS:UNC13D gene mutation had the highest frequency (13/46, 28%). The STXBP2 c.575G>A(p.R192H) and UNC13D c.604C>A(p.L202M) mutations (likely pathogenic) were reported for the first time. The mutation group had a significantly higher level of tumor necrosis factor alpha (TNF-α) than the non-mutation group, while it had a significantly lower level of interferon gamma (IFN-γ) than the non-mutation group (P<0.05). The IL-4 level of the DHM subgroup was higher than that of the non-mutation group, while the IL-4 level of the H-CHM subgroup was lower than that of the DHM group (P<0.0083). The H-CHM subgroup had a significantly lower 1-year overall survival rate than the non-mutation group, the SHM subgroup, and the DHM subgroup (39%±15% vs 85%±6%/86%±7%/91%±9%, P=0.001).
CONCLUSIONS:There is a significant reduction in IFN-γ level in the mutation group. Children with homozygous or compound heterozygous mutation tend to have poorer prognosis, while other mutations do not have a significant impact on prognosis.
