Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers

Clin Infect Dis. 2016 Jul 1;63(1):41-7. doi: 10.1093/cid/ciw160. Epub 2016 May 11.

Abstract

Background: 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.

Methods: We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings.

Results: 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.

Conclusions: 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.

Keywords: Epstein-Barr virus; Epstein-Barr virus smooth muscle tumors; GATA2; chronic active Epstein-Barr disease; hydroa vacciniforme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Child
  • Cytokines / blood
  • DNA, Viral / blood
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / genetics
  • Epstein-Barr Virus Infections* / pathology
  • Epstein-Barr Virus Infections* / virology
  • Female
  • GATA2 Transcription Factor / deficiency*
  • GATA2 Transcription Factor / genetics
  • Herpesvirus 4, Human* / genetics
  • Humans
  • Hydroa Vacciniforme
  • Male
  • Skin Neoplasms* / complications
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / virology
  • Young Adult

Substances

  • Cytokines
  • DNA, Viral
  • GATA2 Transcription Factor
  • GATA2 protein, human