title: Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.
abstract: Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer.
  
  
  
  We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings.
  
  
  
  Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls.
  
  
  
  GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts.
authors.affiliation: Laboratorie of Infectious Diseases.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.affiliation: Laboratorie of Infectious Diseases.
authors.forename: Lesia
authors.initials: L
authors.lastname: Dropulic
authors.affiliation: Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.affiliation: Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.affiliation: Laboratorie of Infectious Diseases.
authors.forename: Tammy
authors.initials: T
authors.lastname: Krogmann
authors.affiliation: Laboratorie of Infectious Diseases.
authors.forename: Kennichi
authors.initials: K
authors.lastname: Dowdell
authors.affiliation: Clinical Services Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Maryland.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hornung
authors.affiliation: Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.
authors.forename: Jana
authors.initials: J
authors.lastname: Lovell
authors.affiliation: Laboratorie of Experimental Transplantation and Immunology Branch.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hardy
authors.affiliation: Laboratorie of Experimental Transplantation and Immunology Branch.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hickstein
authors.affiliation: Laboratorie of Dermatology Branch, Center for Cancer Research.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.affiliation: Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.affiliation: Laboratory of Pathology, National Cancer Institute.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000328:Adult; D002648:Child; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology; D005260:Female; D050989:GATA2 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D006837:Hydroa Vacciniforme; D008297:Male; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology; D055815:Young Adult
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human
keywords: Epstein-Barr virus; Epstein-Barr virus smooth muscle tumors; GATA2; chronic active Epstein-Barr disease; hydroa vacciniforme