New genetic immune disorder identified
- Date:
- June 17, 2015
- Source:
- NIH/National Institute of Allergy and Infectious Diseases
- Summary:
- A new immune disorder has been identified -- DOCK2 deficiency -- named after the mutated gene responsible for the disease. An international team of collaborators studied five children, four boys and one girl, from different ethnic backgrounds who had experienced debilitating infections early in life. The children were diagnosed with combined immunodeficiency, which refers to a group of inherited disorders distinguished by defects in immune system cells called T cells. CIDs also may affect other cells of the immune system, including B cells.
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Researchers funded by the National Institutes of Health (NIH) have identified a new immune disorder--DOCK2 deficiency--named after the mutated gene responsible for the disease. An international team of collaborators studied five children, four boys and one girl, from different ethnic backgrounds who had experienced debilitating infections early in life. The children were diagnosed with combined immunodeficiency (CID), which refers to a group of inherited disorders distinguished by defects in immune system cells called T cells. CIDs also may affect other cells of the immune system, including B cells.
By sequencing the children's genomes, the researchers discovered that mutations in a gene called DOCK2 ultimately cause this particular CID. In laboratory tests, T cells and B cells from the five children had impaired ability to move in response to infection-related stimuli, and anti-viral responses were impaired in many cell types. These observations highlight the importance of DOCK2 in a healthy immune system, and understanding its role may inform the study of more common immune system disorders and the body's response to infection, according to the study investigators.
Three of the children were successfully treated with bone marrow transplants, which replaced the defective immune cells with those of a healthy donor. This finding demonstrates that early screening for CID to identify patients with DOCK2 deficiency can potentially prevent life-threatening infection early in life, as it did for one of these children, who was screened for severe combined immune deficiency (SCID) at birth. Furthermore, identifying causative genes underlying CIDs, such as DOCK2, may enable researchers to develop targeted therapies.
Story Source:
Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.
Journal Reference:
- Kerry Dobbs, Cecilia Domínguez Conde, Shen-Ying Zhang, Silvia Parolini, Magali Audry, Janet Chou, Emma Haapaniemi, Sevgi Keles, Ivan Bilic, Satoshi Okada, Michel J. Massaad, Samuli Rounioja, Adel M. Alwahadneh, Nina K. Serwas, Kelly Capuder, Ergin Çiftçi, Kerstin Felgentreff, Toshiro K. Ohsumi, Vincent Pedergnana, Bertrand Boisson, Şule Haskoloğlu, Arzu Ensari, Michael Schuster, Alessandro Moretta, Yuval Itan, Ornella Patrizi, Flore Rozenberg, Pierre Lebon, Janna Saarela, Mikael Knip, Slavé Petrovski, David B. Goldstein, Roberta E. Parrott, Berna Savas, Axel Schambach, Giovanna Tabellini, Christoph Bock, Talal A. Chatila, Anne Marie Comeau, Raif S. Geha, Laurent Abel, Rebecca H. Buckley, Aydan İkincioğulları, Waleed Al-Herz, Merja Helminen, Figen Doğu, Jean-Laurent Casanova, Kaan Boztuğ, Luigi D. Notarangelo. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections. New England Journal of Medicine, 2015; 372 (25): 2409 DOI: 10.1056/NEJMoa1413462
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