PLCG2 Mutation Causes Rare Immune Disease

Investigators at the NIH have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function. Symptoms of this condition include immune deficiency, autoimmunity, inflammatory skin disorders, and cold-induced hives, a condition known as cold urticaria. The study was led by Dr. Joshua Milner, in the Laboratory of Allergic Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), and Dr. Daniel Kastner, scientific director at the National Human Genome Research Institute (NHGRI). The work was published online on January 11, 2012 in the New England Journal of Medicine. The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID. "Investigating rare diseases gives researchers more clues about how the healthy immune system functions," says NIAID Director Dr. Anthony S. Fauci. "More importantly, identifying the genetic cause of these disorders opens up possibilities for better disease management and potentially a cure for people who may have spent their entire lives debilitated by severe and unexplained symptoms." The NIH study involved 27 people from three separate families who all suffered from an inherited form of cold urticaria, an allergic disease characterized by the formation of itchy, sometimes painful hives, episodes of fainting and, in certain cases, life-threatening reactions in response to cold temperatures. Blood sample analysis revealed that many patients produced antibodies to their own cells and tissues (autoantibodies), making them more susceptible to developing autoimmune disease.