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Biologists Crack Genetic Code for Specialized Spider Silk

Defects in a single gene can result in two immune system disorders that leave affected individuals vulnerable to frequent or unusually severe infections, according to new findings reported in the August issue of Nature Genetics. The discovery may lead to new diagnostic tests for these two inherited conditions ?immunoglobulin A (IgA) deficiency and common variable immunodeficiency (CVID). Currently, doctors diagnose the conditions by measuring immunoglobulin levels and excluding other causes for lowered immunoglobulin levels; there are no specific tests to detect the two disorders.

A deficiency of IgA ?an important type of infection-fighting antibody found in tears, saliva and other secretions ?affects 1 in 600 people in the western world; CVID is less common but more severe. Both conditions result in a person being more susceptible to pneumonia and to recurring infections of the ear, sinus and gastrointestinal tract. People with CVID also have an increased risk of developing cancers that affect B cells, cells that produce antibodies. Furthermore, IgA deficiency and CVID can predispose to autoimmune diseases, where the immune system turns against the body’s own tissues and organs.

“Most cases of CVID and IgA deficiency are of unknown cause,?notes Josiah Wedgwood, M.D., Ph.D., of the Clinical Immunology Branch of the National Institute of Allergy and Infectious Diseases (NIAID), the component of the National Institutes of Health that funded the study. “To find a specific molecular defect that is the apparent cause of illness in a substantial subset of individuals with these two diseases is extremely important. Not only will this finding enable us to better diagnose these patients, it provides clues to key biochemical pathways that can lead to immunodeficiencies.?/p>

The study was led by Raif Geha, M.D., and Emanuela Castigli, Ph.D., of the Children’s Hospital Boston. The Boston team found specific mutations in a gene known as TACI, which plays a spe
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