title: Late-onset severe chronic active EBV in a patient for five years with mutations in STXBP2 (MUNC18-2) and PRF1 (perforin 1).
abstract: Severe chronic active Epstein-Barr virus (CAEBV) disease is defined as a severe progressive illness lasting 6 months or longer with infiltration of tissues with EBV-positive lymphocytes, markedly elevated levels of EBV DNA in the blood, and no known immunodeficiency such as HIV. These patients usually have fever, splenomegaly, lymphadenopathy, and may have markedly elevated EBV antibody titers to viral capsid antigen. Although the cause of most cases of severe CAEBV is unknown, one well-documented case was associated with compound heterozygous mutations in PRF1 (perforin 1). Here we report a patient with prolonged severe CAEBV who underwent bone marrow transplant for his disease and subsequently was found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a heterozygous mutation in PRF1 (perforin 1).
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, jcohen@niaid.nih.gov.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.forename: Julie E
authors.initials: JE
authors.lastname: Niemela
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stoddard
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Helen
authors.initials: H
authors.lastname: Heslop
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Kennichi
authors.initials: K
authors.lastname: Dowdell
mesh_terms: D000328:Adult; D017668:Age of Onset; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism*; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D054353:Perforin / Q000235:genetics*; D014775:Virus Activation / Q000235:genetics; D044465:White People; D055815:Young Adult
chemical_list: D015415:Biomarkers; D052118:Lysosomal-Associated Membrane Protein 1; D051938:Munc18 Proteins; C510468:PRF1 protein, human; C497940:STXBP2 protein, human; D054353:Perforin