Study on rapid diagnosis of primary immunodeficiency diseases and their abnormalities in immunologic development

点击翻译按钮获取中文摘要

Regarding rapid diagnosis of primary immunodeficiency diseases and their abnormalities in immunologic development, we have studied on 1)nation-survey of X-linked qgammaglobulinemia(XLA) by flow cytometric assay and genetic analysis, 2)establishment of flow cytometric rapid diagnosis of X-linked lymphoproliferative syndrome(XLP) by generation of a monoclonal antibody against XLP-causative product SAP, 3)international collaboration of genetic diagnosis of primary immunodeficiency diseases, 4)functional analysis of XLA-causative product BTK, 5)clinical and genetic characteristics of primary immunodeficiency diseases. The results obtained here are as follows.1)We demonstrated clinical and mutational features of XLA in Japan, on the basis of data obtained from more than 100 cases of XLA identified by a combined use of flow cytometric assay with genetic analysis. We identified the first case of female XLA, who was caused by skewed inactivation of normal X-chromosome in the female XLA carrier … More .2)We for the first time demonstrated the presence of patients with XLP by a genetic analysis. We newly generated anti-SAP monoclonal antibody, and confirmed its possible use in flow cytometric rapid diagnosis of XLP.3)We conducted international collaboration of genetic diagnosis of primary immunodeficiency diseases, especially of XLP, in Turkey, Korea, Brazil, Iran and China.4)We showed that XLA-causative product BTK play a critical role for signal transduction in activation of B cells. In addition, we found that cytokine production of XLP-derived dendritic cells was comparable to that in normals, but monocytes from XLP patients were deficient regarding their phagocytic and chemotactic capabilities.5)We reported clinically important cases with some primary immunodeficiency diseases. We also searched for adult patients with hypogammaglobulinemia, who had never received genetic analysis. As a result, we found several cases harboring mutations in the causative genes responsible for primary immunodeficiency diseases. Less