国际研究小组发现新的遗传性免疫缺陷

接触：
伯大尼的特里普
bethany.tripp@childrens.harvard.edu
617-919-3110

波士顿（2015年6月18日）& ndash；五家庭的分析揭示了一个以前未知的遗传性免疫缺陷，说领导的一个国际研究小组的研究人员来自波士顿儿童医院。这种情况，与基因突变有关DOCK2，使免疫系统的许多功能叶受影响的孩子打开一个独特的模式的积极性，潜在的致命的感染，在生命的早期。

正如研究人员&mdash；由多布斯和路易吉notarangelo克里，MD，对变态反应和免疫学&mdash波士顿儿童部；今天的报道新英国医学杂志，DOCK2缺乏可能通过新生儿筛查可检出与造血干细胞移植（HSCT）固化。

Genetic immunodeficiencies，such as X-linked severed combined immunodeficiency (X-SCID) or Wiskott-Aldrich syndrome (WAS)，are a group of devastating conditions where mutations to specific genes cause either functional defects in or interfere with production of T-cells and other components of a patient's immune system. These defects increase a patient's susceptibility to a range of severe infections at an early age.

Conditions for which the causative genes are known，such as X-SCID，can be screened for at birth，allowing for early detection and，when appropriate，curative treatment with a hematopoietic stem cell transplant.

"Until recently，a correct diagnosis for babies born with SCID or other combined immunodeficiencies，such as DOCK2 deficiency，could be made only after these babies had developed serious infections，which could lead to death or compromise the efficacy of an HSCT," said Notarangelo，who is a professor of pediatrics at Harvard Medical School. "Newborn screening for these diseases is now available for most babies with SCID born in the USA，and this gives increased chances of definitive cure by performing the transplant while the baby is still well."

In the current study，Notarangelo，Dobbs and their colleagues at the Rockefeller University and the Center for Molecular Medicine in Austria，conducted genetic，genomic and immunological analyses on five patients from Lebanon，Finland，Turkey and Honduras/Nicaragua who early in life demonstrated symptoms indicating a severe but distinctive immunodeficiency，one that left patients susceptible to a broad range of infections but particularly vulnerable to viruses. Three out of the five patients were born of closely related parents，and three were successfully treated by HSCT.

团队通过全基因组测序，所有五例患者有突变的发现DOCK2，mutations that rendered the DOCK2 protein inactive. The mutations had profound effects on multiple aspects of the patients' immune systems，causing a profound decrease in T-cells and defects in T-，B- and natural killer (NK) cell function.

研究数据表明，在DOCK2，which helps immune cells react to external chemical signals，can have a profound effect on several aspects of immunity，including unforeseen affects on how non-immune cells (such as cells of the skin) respond to viruses.

Notarangelo noted that the data expand the field's understanding of the basic molecular mechanisms underlying human immunity，while adding a new diagnostic target for newborn screening.

“Although congenital immunodeficiencies are rare diseases，the study of these disorders has been essential in identifying key mechanisms governing the immune system's development and function，and how it helps fight against infections," he said. "The knowledge gained has also allowed development of new drugs that harness the immune system to treat more common conditions，including tumors and autoimmune diseases."

The study was supported by the National Institute of Allergy and Infectious Diseases (grant number R01AI100887)，the National Center for Research Resources and National Center for Advancing Clinical and Translational Sciences (grant number UL1TR000043)，the Manton Foundation，the European Research Council (starting grant number 310857)，the Austrian Science Fund START program (grant number Y595-B13)，the German Research Foundation (Cluster of Excellence RE-BIRTH grant numbers EXC 62/1 and CRC738)，the New England Newborn Screening Program at the University of Massachusetts Medical School，the Scientific and Research Council of Turkey (grant number 1059B191300622)，the Union Chimique Belge Celltech and Baxter Healthcare.

波士顿儿童医院的'；

Boston Children’s Hospital is home to the world’s largest research enterprise based at a pediatric medical center，where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists，including sevenmembers of the National Academy of Sciences,11members of the Institute of Medicine and10members of the Howard Hughes Medical Institute comprise Boston Children’s research community. Founded as a 20-bed hospital for children，Boston Children’s today is a 397-bed comprehensive center for pediatric and adolescent health care. Boston Children’s is also the pediatric teaching affiliate of Harvard Medical School.For more，visit our Vector and Thriving blogsand follow us on our social media channels: @BostonChildrens，@BCH_Innovation，Facebook and YouTube.

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