Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy

Author:

Lo Bernice12,Zhang Kejian3,Lu Wei12,Zheng Lixin12,Zhang Qian24,Kanellopoulou Chrysi12,Zhang Yu24,Liu Zhiduo5,Fritz Jill M.12,Marsh Rebecca6,Husami Ammar3,Kissell Diane3,Nortman Shannon3,Chaturvedi Vijaya6,Haines Hilary7,Young Lisa R.8,Mo Jun9,Filipovich Alexandra H.6,Bleesing Jack J.6,Mustillo Peter10,Stephens Michael11,Rueda Cesar M.12,Chougnet Claire A.12,Hoebe Kasper12,McElwee Joshua13,Hughes Jason D.13,Karakoc-Aydiner Elif,Matthews Helen F.12,Price Susan12,Su Helen C.24,Rao V. Koneti12,Lenardo Michael J.12,Jordan Michael B.612

Affiliation:

1. Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

2. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

3. Division of Human Genetics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.

4. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

5. Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

6. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.

7. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA.

8. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

9. Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA.

10. Section of Allergy and Immunology, Nationwide Children’s Hospital, Columbus, OH, USA.

11. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.

12. Division of Immunobiology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.

13. Merck Research Laboratories, Merck & Co, Boston, MA, USA.

Abstract

Trafficking from bedside to bench Typically in translational research, a discovery in cell or molecular biology is later exploited to improve patient care. Occasionally, information flows in the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of a protein called LRBA responded dramatically to the drug abatacept (see the Perspective by Sansom). Abatacept contains a segment of a potent inhibitory immune receptor, CTLA4. Experiments prompted by this observation revealed the relationship between the two proteins: LRBA controls the intracellular trafficking and degradation of CTLA4. This information may further improve patient care, because other clinically approved drugs have the desired mechanism of action with potentially fewer side effects. Science , this issue p. 436 ; see also p. 377

Funder

NIH

National Institute of Allergy and Infectious Diseases

American Society of Hematology

Merck, Inc.

Cincinnati Children’s Hospital Medical Center

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Cited by 535 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3