Blood Journal
Leading the way in experimental and clinical research in hematology

SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease

  1. Christine Rivat1,
  2. Claire Booth1,
  3. Maria Alonso-Ferrero1,
  4. Michael Blundell1,
  5. Neil J. Sebire2,
  6. Adrian J. Thrasher1, and
  7. H. Bobby Gaspar1,*
  1. 1 Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom;
  2. 2 Department of Histopathology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom
  1. * Corresponding author; email: h.gaspar{at}


X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SAP and leads to abnormalities of NKT cell development, NK cell cytotoxicity and T dependent humoral function. Curative treatment is limited to allogeneic haematopoietic stem cell transplantation (HSCT). We tested whether HSC gene therapy could correct the multi-lineage defects seen in SAP-/- mice. SAP-/- murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT cell development was significantly higher and NK cell cytotoxicity restored to wild type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T dependent humoral responses to NP-CGG, including germinal centre formation, were restored in SAP transduced mice. We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP-/- mice providing proof of concept for gene therapy in XLP1.

  • Submitted July 26, 2012.
  • Accepted November 11, 2012.