Jeffrey I Cohen1, Lesia Dropulic1, Amy P Hsu2, Christa S Zerbe2, Tammy Krogmann1, Kennichi Dowdell1, Ronald L Hornung3, Jana Lovell2, Nancy Hardy4, Dennis Hickstein4, Edward W Cowen5, Katherine R Calvo6, Stefania Pittaluga7, Steven M Holland2. 1. Laboratorie of Infectious Diseases. 2. Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases. 3. Clinical Services Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Maryland. 4. Laboratorie of Experimental Transplantation and Immunology Branch. 5. Laboratorie of Dermatology Branch, Center for Cancer Research. 6. Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda. 7. Laboratory of Pathology, National Cancer Institute.
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. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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 EBVinfectious 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. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Authors: Emily M Mace; Amy P Hsu; Linda Monaco-Shawver; George Makedonas; Joshua B Rosen; Lesia Dropulic; Jeffrey I Cohen; Eugene P Frenkel; John C Bagwell; John L Sullivan; Christine A Biron; Christine Spalding; Christa S Zerbe; Gulbu Uzel; Steven M Holland; Jordan S Orange Journal: Blood Date: 2013-01-30 Impact factor: 22.113
Authors: Donald C Vinh; Smita Y Patel; Gulbu Uzel; Victoria L Anderson; Alexandra F Freeman; Kenneth N Olivier; Christine Spalding; Stephen Hughes; Stefania Pittaluga; Mark Raffeld; Lynn R Sorbara; Houda Z Elloumi; Douglas B Kuhns; Maria L Turner; Edward W Cowen; Danielle Fink; Debra Long-Priel; Amy P Hsu; Li Ding; Michelle L Paulson; Adeline R Whitney; Elizabeth P Sampaio; David M Frucht; Frank R DeLeo; Steven M Holland Journal: Blood Date: 2009-12-29 Impact factor: 22.113
Authors: Rachel Emma Dickinson; Helen Griffin; Venetia Bigley; Louise N Reynard; Rafiqul Hussain; Muzlifah Haniffa; Jeremy H Lakey; Thahira Rahman; Xiao-Nong Wang; Naomi McGovern; Sarah Pagan; Sharon Cookson; David McDonald; Ignatius Chua; Jonathan Wallis; Andrew Cant; Michael Wright; Bernard Keavney; Patrick F Chinnery; John Loughlin; Sophie Hambleton; Mauro Santibanez-Koref; Matthew Collin Journal: Blood Date: 2011-07-15 Impact factor: 22.113
Authors: Christopher N Hahn; Chan-Eng Chong; Catherine L Carmichael; Ella J Wilkins; Peter J Brautigan; Xiao-Chun Li; Milena Babic; Ming Lin; Amandine Carmagnac; Young K Lee; Chung H Kok; Lucia Gagliardi; Kathryn L Friend; Paul G Ekert; Carolyn M Butcher; Anna L Brown; Ian D Lewis; L Bik To; Andrew E Timms; Jan Storek; Sarah Moore; Meryl Altree; Robert Escher; Peter G Bardy; Graeme K Suthers; Richard J D'Andrea; Marshall S Horwitz; Hamish S Scott Journal: Nat Genet Date: 2011-09-04 Impact factor: 38.330
Authors: Mark Parta; Jennifer Cuellar-Rodriguez; Alexandra F Freeman; Juan Gea-Banacloche; Steven M Holland; Dennis D Hickstein Journal: J Clin Immunol Date: 2016-12-06 Impact factor: 8.317
Authors: Kathleen E Sullivan; Hamid Bassiri; Ahmed A Bousfiha; Beatriz T Costa-Carvalho; Alexandra F Freeman; David Hagin; Yu L Lau; Michail S Lionakis; Ileana Moreira; Jorge A Pinto; M Isabel de Moraes-Pinto; Amit Rawat; Shereen M Reda; Saul Oswaldo Lugo Reyes; Mikko Seppänen; Mimi L K Tang Journal: J Clin Immunol Date: 2017-08-07 Impact factor: 8.317
Authors: Matthew K Howe; Kennichi Dowdell; Hye Sun Kuehn; Qingxue Li; Geoffrey T Hart; Doreen Garabedian; Kelly Liepshutz; Amy P Hsu; Hua Su; Julie E Niemela; Jennifer L Stoddard; Gulbu Uzel; Evan Shereck; Laura Schulz; Tatyana Feldman; Sergio D Rosenzweig; Eric O Long; Lesia Dropulic; Jeffrey I Cohen Journal: J Infect Dis Date: 2020-09-01 Impact factor: 5.226
Authors: Melissa A Levoska; Jeffrey I Cohen; Irini Manoli; Chyi-Chia Richard Lee; Steven S T Ching; Jessica Shand; Deborah Tamura; Kenneth H Kraemer; John J DiGiovanna Journal: J Am Acad Dermatol Date: 2017-09-28 Impact factor: 11.527
Authors: Thomas Mika; Deepak Vangala; Matthias Eckhardt; Paul La Rosée; Christoph Lange; Kai Lehmberg; Charlotte Wohlschläger; Saskia Biskup; Ilka Fuchs; Jasmin Mann; Stephan Ehl; Klaus Warnatz; Roland Schroers Journal: Front Immunol Date: 2021-05-10 Impact factor: 7.561