New Genetic Mechanism of Immune Deficiency Discovered

Researchers at National Jewish Health have discovered a novel genetic mechanism of immune deficiency. Magdalena M. Gorska, M.D., Ph.D., and Rafeul Alam, M.D., Ph.D., identified a mutation in Unc119 that causes an immunodeficiency known as idiopathic CD4 lymphopenia. Unc119 is a signaling protein that activates and induces T-cell proliferation. The mutation impairs Unc119’s ability to activate T-cells. Dr. Gorska presented the findings on April 20, 2012 at Translational Science 2012, an NIH-funded conference in Washington D.C. “A better understanding of the molecular mechanisms associated with this mutation will improve diagnosis and pave the way for development of new therapies,” said Dr. Gorska. Drs. Gorska and Alam previously published their findings in the February 9, 2012 issue of Blood, and Dr. Gorska delivered a Presidential Plenary lecture on the topic at the annual meeting of the American Academy of Allergy Asthma & Immunology. Nearly a decade ago, Drs. Alam and Gorska identified Unc119 as a novel activator of SRC-type tyrosine kinases, important regulators of cellular function. Since then, they have published numerous papers in which they characterized the function of this protein in various aspects of the immune system. Idiopathic CD4 lymphopenia is a rare and heterogeneous syndrome defined by low levels of CD4 T-cells in the absence of HIV infection, which predisposes patients to infections and malignancies. Recent research by others had linked the syndrome to reduced activation of the SRC-type kinase known as Lck. The latter kinase is involved in T-cell development, activation, and proliferation. So, Drs. Alam and Gorska thought Unc119, an activator of Lck, might be involved.