title: Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein-Barr virus infection.
abstract: Chronic active Epstein-Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan. kanegane@med.u-toyama.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Otsubo
authors.affiliation: Department of Pediatrics, Medical Science Cluster, Research and Education Faculty, Kochi University, Nankoku, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.affiliation: Department of Pediatrics, Kansai Medical University, Hirakata, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.affiliation: Department of Pediatrics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000293:Adolescent; D000328:Adult; D056735:Autoimmune Lymphoproliferative Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000503:physiopathology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism / Q000821:virology; D008297:Male; D009154:Mutation / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D022821:RNA Splice Sites; D019014:fas Receptor; D016753:Interleukin-10