Common variable immunodeficiency (common variable immune deficiency) - Gen TNFRSF13B
Common variable immunodeficiency (CVID) is a disorder that affects the immune system. People with CVID are prone to infection by bacteria or, less frequently, viruses and often develop recurrent infections, especially in the lungs, sinuses and ears. Often, affected individuals develop pneumonia. Eventually, recurrent infections can lead to chronic lung disease. Affected individuals may also develop an infection or inflammation of the gastrointestinal tract, which can cause diarrhea and weight loss. In some individuals, the abnormal accumulation of immune cells causes lymphadenopathy or splenomegaly. In addition, immune cells can accumulate in other organs, forming granulomas.
Approximately 25% of individuals with common variable immunodeficiency have an autoimmune disorder. The blood cells are the most affected by autoimmune episodes in common variable immunodeficiency. Autoimmune disorders that occur more frequently are immune thrombocytopenic purpura, autoimmune hemolytic anemia and rheumatoid arthritis. In addition, affected individuals are at increased risk of developing certain cancers, including non - Hodgkin lymphoma and, less commonly, stomach cancer. Individuals with CVID may begin to show signs and symptoms of the disease at any time between childhood and adulthood. Although life expectancy of these individuals varies depending on the severity and frequency of diseases that present, most live in adulthood.
In 90% of cases of common variable immunodeficiency, the cause is unknown. It is likely to be due to both genetic and environmental factors. While specific environmental factors are unclear, it is believed that genetic influences on CVID are mutations in genes involved in the development and function of B cells of the immune system. When mature B cells produce immunoglobulins binding to foreign matter, marking them for destruction. Mutations in genes associated with CVID result in dysfunctional B cells can not produce sufficient quantities of antibodies.
In about 10% of the remaining cases, the process may be due to changes in at least 13 genes. These genes include CD19, CD81, CR2, ICOS, IKZF1, IL21, LRBA, MS4A1, NFKB1, NFKB2, PRKCD, TNFRSF13B, TNFRSF13C. Of these, the most common mutations occur in the gene TNFRSF13B (Tumor necrosis factor receptor superfamily member 13B), located on the short arm of chromosome 17 (17p11.2). This gene encodes a protein called TACI. The TACI protein is on the surface of B cells of the immune system. These cells help protect the body against infection from foreign agents such as bacteria and viruses. When mature B cells, produce antibodies that bind to strangers, marking them for destruction agents. Through interactions with other proteins, the TACI promotes cell signaling plays a role in the maturation and survival of B cells, and is involved in antibody production. CVID have individuals with a deficiency of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM). Some have a deficiency of the three antibodies, while others lack only IgG and IgA. Deficiency of these antibodies makes it difficult for those affected to fight infection.
They have identified more than 25 mutations in the gene TNFRSF13B associated with common variable immunodeficiency (CVID). Genetic mutations in TNFRSF13B seem to express the disease in some people, but do not seem to lead to immune problems in others. Most mutations change amino acids in the TACI protein. The most frequent mutation replaces the amino acid cysteine for the amino acid arginine at position 104 in TACI (Cys104Arg or C104R) protein. This mutation disrupts the ability of TACI to interact with other proteins, which alters cell signaling and inhibits the maturation of normal B cells and antibody production. Deficiency of certain antibodies makes it difficult for those affected to fight infection. Abnormal and deficient immune responses probably eventually contribute to increased cancer risk.
Most cases of CVID are sporadic and occur in people with no apparent history of the disease in your family. It is likely that these cases are due to a complex interaction of environmental and genetic factors. In some families, the disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. In rare cases, the disease is inherited as an autosomal dominant, which means that a copy of an altered gene in each cell is sufficient to express the disease. Not all people who inherit a genetic mutation associated with common variable immunodeficiency disease express. In many cases, affected children have an affected parent who shares the same mutation. It is likely that additional genetic or environmental factors are needed for the disease to be expressed.
Tests in IVAMI: in IVAMI perform detection of mutations associated with common variable immunodeficiency (CVID), by complete PCR amplification of the exons of the gene TNFRSF13B, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).