2003 Fiscal Year Final Research Report Summary
Molecular pathology of X-linked lymphopro liferative disease : Towards the development of the gene therapy
| Project/Area Number |
14570722
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SUMAZAKI Ryo University of Tsukuba, Institute of Clinical Medicine, Associate Professor, 臨床医学系, 助教授 (40163050)
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| Co-Investigator(Kenkyū-buntansha) |
ONODERA Masashi University of Tsukuba, Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (10334062)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Epstein-Barr Virus / X-linked lymphoproliferative disease / SAP(SLAM-associated protein) / SH2D1A / primary immunodeficiency / T lymphocytes / early diagnosis / vasculitis |
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| Research Abstract |
X-linked lymphoproliferative disease (XLP, MIM 308240) is a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection. Recently, an SH2-domain-encoding gene, SH2DIA/SAP was identified as the causative gene of XLP and the genetic diagnosis applied to the family members of XLP patients provides the tool for finding pre-symptomatic XLP patients. However, the easy method for definitive diagnosis and the therapeutic strategy for these pre-symptomatic patients are largely unknown. Especially, because of the poor prognosis in symptomatic XLP patients, early diagnosis and treatment for the presymptomatic patients are clinically of great importance. The research was performed to solve these problems based on the molecular pathology of XLP patients.
<Results>
1. We have establish the new and easy method for the XLP diagnosis, using the specific monoclonal antibody against recombinant SAP protein and flow-cytometric detection of SAP protein in the lymphocytes obtained from patient's blood.
2. We have found that SAP protein dosage is regulated by the lymphocyte activation and that SAP-deficient lymphocytes cannot activate killer function to target cells.
3. Two XLP patients, who had survived the EBV infection and kept good health for more than 5 years after EBV infection, suddenly suffered from severe lymphocytic vasculitis.
<Discussion and Conclusions>
Our study indicates that easy flow-cytometric analysis provides definitive XLP diagnosis without time-consuming and expensive mutational analysis. Inducible SAP expression is needed for the gene therapy for the XLP patients. Apparently healthy persons with SAP mutations are very dangerous to severe lymphocytic vasculitis and thus, almost all pre-symptomatic XLP patients may need blood stem cell transplantation.
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Research Products
(14 results)
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[Journal Article] Activation-dependent T cell expression of the X-linked lymphoproliferative disease gene product SLAM-associated protein and its assessment for patient detection2003
Author(s)
Shinozaki K, Kanegane H, Matsukura H, Sumazaki R, Tsuchida M, Makita M, Kimoto Y, Kanai R, Tsumura K, Kondoh T, Moriuchi H, Miyawaki T
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Journal Title
International Immunology Vol 14-No10
Pages: 1215-1223
Description
「研究成果報告書概要(欧文)」より
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