Immunologic Research

, Volume 42, Issue 1–3, pp 145–159 | Cite as

X-linked lymphoproliferative disease (XLP): a model of impaired anti-viral, anti-tumor and humoral immune responses

  • Hamid Bassiri
  • W. C. Janice Yeo
  • Jennifer Rothman
  • Gary A. Koretzky
  • Kim E. NicholsEmail author


A major focus of our research is to understand the molecular and cellular basis of X-linked lymphoproliferative disease (XLP), a rare and often fatal immunodeficiency caused by mutations in the SH2D1A gene, which encodes the adaptor molecule SAP. Recently, we observed that SAP is essential for the development of natural killer T (NKT) cells, a lymphocyte population that participates in protection against certain tumors, infections, and autoimmune states. In this review, we describe the approaches that we are taking to understand the role of SAP in immune cells, including NKT cells. By using SAP as the focal point of our studies, we hope to identify novel signaling pathways that could be targeted to improve the treatment for patients with XLP as well as more common disorders, such as autoimmunity and cancer.


Immunodeficiency X-linked lymphoproliferative disease Epstein Barr virus Signal transduction Adaptor molecule Natural killer T cell 



We thank Mitchell Kronenberg, Pamela Schwartzberg, Juan Carlos Zuniga-Pflucker, Kirin Brewery, and the National Institutes of Health (NIH) Tetramer Facility for providing reagents. We also thank Justina Stadanlick for editorial assistance with this manuscript. This work was funded by grants from the NIH and the XLP Research Trust.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hamid Bassiri
    • 1
  • W. C. Janice Yeo
    • 2
  • Jennifer Rothman
    • 3
  • Gary A. Koretzky
    • 4
    • 5
    • 6
  • Kim E. Nichols
    • 2
    Email author
  1. 1.Infectious Diseases Fellowship Training ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Division of OncologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.Hematology/Oncology Fellowship Training ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  4. 4.Department of Pathology & Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Abramson Family Cancer Research InstitutePhiladelphiaUSA
  6. 6.Division of Rheumatology, Department of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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