What are the genetic changes related to common variable immune deficiency ?
CVID is believed to result from mutations in genes that are involved in the development and function of immune system cells called B cells. B cells are specialized white blood cells that help protect the body against infection. When B cells mature, they produce special proteins called antibodies (also known as immunoglobulins). These proteins attach to foreign particles, marking them for destruction. Mutations in the genes associated with CVID result in dysfunctional B cells that cannot make sufficient amounts of antibodies.  People with CVID have a shortage (deficiency) of specific antibodies called immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM). Some have a deficiency of all three antibodies, while others are lacking only IgG and IgA. A shortage of these antibodies makes it difficult for people with this disorder to fight off infections. Abnormal and deficient immune responses over time likely contribute to the increased cancer risk. In addition, vaccines for diseases such as measles and influenza do not provide protection for people with CVID because they cannot produce an antibody response.  Mutations in at least 10 genes have been associated with CVID. Approximately 10 percent of affected individuals have mutations in the TNFRSF13B gene. The protein produced from this gene plays a role in the survival and maturation of B cells and in the production of antibodies. TNFRSF13B gene mutations disrupt B cell function and antibody production, leading to immune dysfunction. Other genes associated with CVID are also involved in the function and maturation of immune system cells, particularly of B cells; mutations in these genes account for only a small percentage of cases.  In most cases of CVID, the cause is unknown, but it is likely a combination of genetic and environmental factors.