title: Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant.
abstract: Vasculitis occurs rarely in association with X-linked lymphoproliferative disease (XLP). There are four published cases of non-EBV XLP-associated cerebral vasculitis reported, none of whom have survived without major cognitive impairment.
  
  
  METHODS
  A 9-year old boy initially presented aged 5 years with a restrictive joint disease. He subsequently developed dysgammaglobulinemia, episodic severe pneumonitis, aplastic anaemia, gastritis and cerebral vasculitis. A diagnosis of XLP was made, based on flow cytometric analysis and the identification of a novel mutation in SH2D1A, c.96G>C. No peripheral blood lymphocyte clonal proliferation was identified and he was EBV negative, although human herpes virus-7 (HHV7) was detected repeatedly in his cerebrospinal fluid. He underwent a reduced intensity unrelated umbilical cord blood transplant, but failed to engraft. A second 5/6 matched cord gave 100 % donor engraftment. Complications included BK virus-associated haemorrhagic cystitis, a possible NK-cell mediated immune reconstitution syndrome and post-transplant anti-glomerular basement membrane disease, the latter treated with cyclophosphamide and rituximab. At +450 days post-transplant he is in remission from his vasculitis and anti-glomerular basement membrane disease, and HHV-7 has remained undetectable.
  
  
  CONCLUSIONS
  This is the second published description of joint disease in XLP, and only the fourth case of non-EBV associated cerebral vasculitis in XLP, as well as being the first to be successfully treated for this manifestation. This case raises specific questions about vasculitis in XLP, in particular the potential relevance of HHV-7 to the pathogenesis.
authors.affiliation: Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Australia.|School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Gray
authors.affiliation: School of Women's and Children's Health, University of New South Wales, Sydney, Australia.|Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: O'Brien
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, Australia.|St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Mayura
authors.initials: M
authors.lastname: Wagle
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, Australia.|St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, Australia.|St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Umaimainthan
authors.initials: U
authors.lastname: Palendira
authors.affiliation: Department of Medical Genetics, Sydney Children's Hospital, Randwick, Australia.|Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Roscioli
authors.affiliation: Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Choo
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Randwick, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Australia.|School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Ziegler
authors.affiliation: Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Australia. frith.katie@gmail.com.|School of Women's and Children's Health, University of New South Wales, Sydney, Australia. frith.katie@gmail.com.
authors.forename: Katie
authors.initials: K
authors.lastname: Frith
mesh_terms: D001315:Australia; D002648:Child; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D006680:HLA Antigens / Q000276:immunology; D016199:Herpesvirus 7, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007109:Immunity / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007592:Joint Diseases / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000502:physiology* / Q000637:transplantation / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D011183:Postoperative Complications / Q000188:drug therapy*; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage; D019349:Roseolovirus Infections / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D020293:Vasculitis, Central Nervous System / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*
chemical_list: D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000069283:Rituximab; D003520:Cyclophosphamide
keywords: HHV-7; X-linked lymphoproliferative disease (XLP); haematopoietic stem cell transplant; vasculitis