Medical research into XLP is still very much in its infancy but we do ensure that the money you donated is only spent on the very ‘best science’. Every application received in fully peer reviewed by external experts who pass on their advice to our board of trustees. This trustees then decides which projects would give the best scientific outcomes for XLP and the best value for money. Equally importantly, we demand absolute clarity regarding how grants are spent, and monitor and evaluate carefully.The external experts decide on which projects offer the best scientific outcomes for XLP and the best value for money. Based on their opinion the trustees then decide which projects to fund. Equally importantly, we demand absolute clarity regarding how grant monies will be spent, and have in place monitoring systems that will enable us to evaluate carefully the progress of the research work undertaken will your valuable donations.

You can download a copy of our medical research strategy from here.

Download: Medical Research Strategy

There is also a glossary of medical terms, related to XLP, available here.

Glossary

The charity made its first awards in the summer of 2007. We expect to be in a position to receive further proposals later in 2007 or early 2008. If you would like notification of when we will be going through our next funding round then please contact us at the office.

Current Projects

”Regulation of NKT cell development and function by SAS, the protein defective in X-linked lymphoproliferative disease”

Kim Nichols, MD Children’s Hospital of Philadelphia, United States of America. £73,305 over two years. Awarded 2007.

Abstract

Our laboratory is studying proteins that regulate the activity of T lymphocytes, white blood cells that are essential in the immune response against specific pathogens, such as viruses. By identifying molecules that control host protective mechanisms, we hope to develop improved therapies for patients suffering from severe virus infections and virus-associated cancers. We have made progress by studying X-linked lymphoproliferative disease (XLP), a rare and often fatal immunodeficiency characterized by a decreased ability to control Epstein-Barr virus infection, a reduced production of specialized proteins known as antibodies and an increased risk to develop lymphoma. Previously, we identified SHZDlA, the gene that is abnormal in XLP patients. SHZDlA encodes for a protein known as SAP, which regulates the functions of T lymphocytes. Recently, we observed that SAP is required for the development of a potent but poorly understood subset of T lymphocytes known as natural killer T (IVKT) cells. Currently, our research is focused on understanding how SAP controls NKT cell development and establishing whether this adaptor regulates mature NKT cell functions. We are also examining how the absence of IVKT cells contributes to the abnormal antiviral immune responses that occur in XLP patients and SAP-deficient mice. These studies will increase our understanding of NKT cell biology and may provide insights into how LIKT cells can be expanded and activated to enhance host immunity.

“Characterising the Phenotype, Specificity and Function of Virus-Specific CD8+ T cells in SAP-deficient XLP patients”

Dr Stuart Tangye and Dr Umamainthan Palendira
Garvan Institute, Darlinghurst, NSW, Australia. £30,000 over two years. Awarded 2007.

Abstract

X-linked lymphoproliferative disease (XLP) is an inherited disease. The gene defect results in the absence of a protein that is involved in signalling through numerous receptors on the surface of white blood cells. These receptors may be crucial for the function of cytotoxic T lymphocytes, a population of white blood cells that are important for anti-viral immune responses and for tumour clearance. One major problem for XLP patients is their increased sensitivity to infection with Epstein Barr Virus (EBV), a virus which causes asymptomatic infection in the majority of the population, but can occasionally cause self-limiting infectious mononucleosis (Glandular fever). Exposure to EBV is often fatal in XLP patients and even those who survive acute virus infection often go on to develop further complications such as lymphoma, a cancer of immune cells. We aim to investigate why XLP patients are particularly susceptible to infection with EBV. We will achieve this by characterising the differences in the function of cytotoxic white blood cells collected from XLP patients and from healthy individuals. We will also determine why XLP patients are able to respond to common viruses such as Influenza virus. This study will provide a greater understanding of why XLP patients are particularly susceptible to one particular virus, which causes widespread tissue damage of often death in these patients. The findings from this study may aid in the development of new treatmentsltherapies for XLP patients.

“Molecular characterization of XLP-like diseases”

Sylvain Latour, Christelle Lenoir and Stéphanie Rigaud
Inserm Unit 768, Hôpital Necker-Enfants Malades, Paris, France. €55,000 over two years. Awarded 2007.

Abstract

The X-linked lymphoproliferative syndrome (XLP) or Purtilo syndrome is a rare inherited immunodeficiency that is characterized by an inappropriate immune response to Epstein-Barr virus (EBV) infection. Mutations in the genes SAP and XIAP underlie most of the patients with familial XLP disease. We have recently established that both XIAP and SAP deficiency lead to a specific defect in a particular lymphocyte subpopulation, the NKT lymphocytes.

The aim of this proposal is : There is a significant number of patients presenting an EBV-associated lymphoproliferative syndrome (diagnosed as an XLP-like disease) that are not carrying mutations in SAP nor XIAP. In these patients, the genetic origin of the condition is unknown suggesting that other genes may account for the pathology in these patients. The identification of the gene defect (s) that cause these related syndromes will be undertaken. This study will help identify people who may suffer from XLP-like conditions.