Hemophagocytic lymphohistiocytosis caused by STAT1 gain-offunction mutation is not driven by interferon-γ:A case report  

作　　者：Nan Liu Fen-Ying Zhao Xiao-Jun Xu 

机构地区：[1]Department of Hematology-oncology,Children’s Hospital,Zhejiang University School of Medicine,Hangzhou 310003,Zhejiang Province,China

出　　处：《World Journal of Clinical Cases》2020年第23期6130-6135,共6页世界临床病例杂志

摘　　要：BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a life-threatening hyperinflammatory syndrome caused by many genetic defects.STAT1 is a DNAbinding factor that regulates gene transcription.HLH caused by STAT1 gain-offunction(GOF)mutations has rarely been reported and its clinical manifestations and mechanisms are not clearly defined.CASE SUMMARY A 2-year-old boy presented to our hospital with recurrent fever for>20 d.The patient had a personal history of persistent oral candidiasis and inoculation site infection during the past 2 years.Hepatosplenomegaly was noted.Complete blood cell count showed severe anemia,thrombocytopenia and neutropenia.Other laboratory tests showed liver dysfunction,hypertriglyceridemia and decreased fibrinogen.Hemophagocytosis was found in the bone marrow.Chest computed tomography showed a cavitary lesion.Tests for fungal infection were positive.Serum T helper(Th)1/Th2 cytokine determination demonstrated moderately elevated levels of interleukin(IL)-6 and IL-10 with normal interferon(IFN)-γconcentration.Mycobacterium bovis was identified in bronchoalveolar lavage fluid by polymerase chain reaction.Genetic testing identified a heterozygous mutation of c.1154C>T causing a T385M amino acid substitution in STAT1.Despite antibacterial and antifungal therapy,the febrile disease was not controlled.The signs of HLH were relieved after HLH-94 protocol administration,except fever.Fever was not resolved until he received anti-tuberculosis therapy.Hematopoietic stem cell transplantation was refused and the patient died six months later due to severe pneumonia.CONCLUSION Patients with STAT1 GOF mutation have broad clinical manifestations and may develop HLH.This form of HLH presents with normal IFN-γlevel without cytokine storm.

关 键 词：Hemophagocytic lymphohistiocytosis Signal transducer and activator of transcription 1 GAIN-OF-FUNCTION Interferon gamma Mycobacterial disease Case report 

分 类 号：R725.5[医药卫生—儿科]