Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome
نویسندگان
چکیده
منابع مشابه
Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome.
Loss of CD40 ligand (CD40L) expression or function results in X-linked hyper-immunoglobulin (Ig)M syndrome (X-HIGM), characterized by recurrent infections due to impaired immunoglobulin class-switching and somatic hypermutation. Previous attempts using retroviral gene transfer to correct murine CD40L expression restored immune function; however, treated mice developed lymphoproliferative diseas...
متن کاملAnalysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting.
Subjects with X-linked hyper-IgM syndrome (X-HIgM) have a markedly reduced frequency of CD27(+) memory B cells, and their Ig genes have a low level of somatic hypermutation (SHM). To analyze the nature of SHM in X-HIgM, we sequenced 209 nonproductive and 926 productive Ig heavy chain genes. In nonproductive rearrangements that were not subjected to selection, as well as productive rearrangement...
متن کاملNonmyeloablative hematopoietic stem cell transplant for X-linked hyper-immunoglobulin m syndrome with cholangiopathy.
OBJECTIVE X-linked hyper-immunoglobulin M (X-HIM) syndrome is a rare genetic immunodeficiency syndrome caused by mutations in the gene encoding CD40 ligand (CD40L, CD154). Allogeneic hematopoietic stem cell transplantation (HSCT) offers the prospect of immune reconstitution in X-HIM syndrome. Standard HSCT using high-dose chemoradiotherapy can be followed by serious hepatic problems, including ...
متن کاملCD40 ligand-deficient T cells from X-linked hyper-IgM syndrome carriers have intrinsic priming capability.
Deficiency in CD40 ligand (CD40L) expression is associated with impaired T cell immunity in mouse models and in humans. Previous studies have indicated that this is due to the failure of induction of extrinsic costimulatory molecules. However, other studies have suggested that CD40L is an intrinsic costimulatory molecule. The X-linked hyper-IgM syndrome (XHIM) is a primary immunodeficiency caus...
متن کاملPartial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand.
X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval...
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ژورنال
عنوان ژورنال: Cell Reports
سال: 2018
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.04.103