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
ZHANG Yao, TANG Yong-Min
Pediatric Hematology and Oncology Center, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310003, China
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.
ZHANG Yao,TANG Yong-Min. 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[J]. CJCP, 2020, 22(6): 620-625.
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