title: X-linked lymphoproliferative syndrome presenting with systemic lymphocytic vasculitis.
abstract: X-linked lymphoproliferative syndrome (XLP) is a rare, often fatal, primary immunodeficiency disease characterized by an abnormal response to Epstein-Barr virus (EBV) infection. The gene responsible for XLP has been identified as SH2D1A/DSHP/SLAM-associated protein (SAP). The major clinical manifestations include fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia. Affected males uncommonly present with lymphocytic vasculitis in addition to aplastic anemia. In this study, we describe a Japanese XLP patient who presented with hypogammaglobulinemia following acute EBV-induced infectious mononucleosis in the infancy and later had systemic lymphocytic vasculitis and hemophagocytic lymphohistiocytosis in the adulthood, which resolved by steroid pulse therapy. The patient's SAP gene was found to harbor a missense mutation (His8Asp), presumably resulting in defective expression of SAP in T cells. Biopsy specimens of lung and skin disclosed that CD8+ T cells predominantly infiltrated vascular vessels. However, immunohistochemical examination showed that EBV-infected cells were not identifiable in the vessels. We propose that T-cell-mediated immune dysregulation in XLP can cause vasculitis by EBV infection-unrelated mechanism.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. kanegane@ms.toyama-mpu-ac.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shichijo
authors.forename: Kunio
authors.initials: K
authors.lastname: Tomimasu
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D007244:Infectious Mononucleosis / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D013256:Steroids / Q000627:therapeutic use; D014657:Vasculitis / Q000209:etiology* / Q000276:immunology
chemical_list: D013256:Steroids