Common Variable Immunodeficiency (CVID) is a disorder of the immune system where the body has difficulty producing the specific proteins, known as antibodies, that are needed to fight infections. It is one of the most frequently diagnosed primary immunodeficiencies, meaning the condition is not caused by another illness or medication. It is “common” because it is diagnosed more often than many other primary immunodeficiencies, affecting about 1 in 25,000 people. The term “variable” highlights how the condition’s severity and specific health effects can differ significantly from one person to another.
Symptoms and Associated Conditions
The most defining characteristic of CVID is an increased susceptibility to recurrent infections, particularly those caused by bacteria. Individuals often experience repeated episodes of sinusitis, bronchitis, ear infections, and pneumonia. While many people are diagnosed in adulthood, symptoms can first appear in childhood or during the teenage years.
CVID is also linked to a range of non-infectious complications from immune system dysregulation. A significant number of individuals develop autoimmune disorders, where the immune system mistakenly attacks the body’s own tissues. This can lead to conditions such as immune thrombocytopenic purpura, where platelets are destroyed, or autoimmune hemolytic anemia, which affects red blood cells. In approximately 20% of cases, an autoimmune issue is the first sign of the underlying immunodeficiency.
Gastrointestinal problems are also frequently reported, with symptoms like chronic diarrhea, abdominal pain, nausea, and unintended weight loss. Another potential complication is the formation of granulomas, which are small clusters of inflammatory cells that can accumulate in organs like the lungs, spleen, or liver. People with CVID also have a heightened risk of developing certain cancers, most notably lymphoma.
Causes and Genetic Links
For the vast majority of individuals, estimated at around 90%, the specific cause of their CVID remains unknown; these cases are referred to as sporadic. Researchers believe the condition likely arises from a combination of genetic and environmental factors, though the environmental triggers have not been identified.
In the remaining cases, a direct genetic link has been established. Although most people with CVID do not have a family history of the disorder, it can be inherited. Mutations in several different genes can lead to CVID. These genetic changes interfere with the proper function and development of the immune system’s B-cells.
B-cells are the white blood cells responsible for maturing into plasma cells, which produce antibodies. In CVID, this maturation process is flawed. Genes such as ICOS, TACI (also known as TNFRSF13B), and CD19 are among those that, when mutated, have been shown to disrupt the signals required for B-cells to activate and produce a sufficient supply of immunoglobulins.
The Diagnostic Process
Diagnosing CVID can be a lengthy process because its primary symptoms, recurrent infections, are common in the general population and can be mistaken for other health issues. A diagnosis relies on a combination of specific laboratory findings and the exclusion of other possible causes for the immune system’s dysfunction.
A CVID diagnosis is based on a set of blood tests that measure the levels of different types of antibodies, or immunoglobulins. A definitive diagnosis requires a significantly reduced level of immunoglobulin G (IgG), which is the most abundant antibody in the blood. In addition to low IgG, there must also be a low level of at least one other major antibody class, either immunoglobulin A (IgA) or immunoglobulin M (IgM).
Another step is assessing the body’s functional immune response, which is often done by checking the response to vaccines. A person with CVID will show a poor or absent ability to produce specific antibodies after receiving a vaccination, such as one for tetanus or pneumonia. Finally, physicians must rule out other conditions or external factors that can cause low antibody levels to confirm the diagnosis.
Treatment and Management Strategies
The primary treatment for CVID is lifelong immunoglobulin (Ig) replacement therapy. This treatment supplies the body with the antibodies it is unable to produce on its own, helping reduce the frequency and severity of infections. The immunoglobulin is prepared from the plasma of thousands of screened blood donors, providing a broad spectrum of antibodies to protect against various pathogens.
There are two main methods for administering this therapy. Intravenous immunoglobulin (IVIG) is delivered directly into a vein at a hospital or infusion center, typically every three to four weeks. The alternative is subcutaneous immunoglobulin (SCIG), which is infused into the fatty tissue just under the skin. SCIG infusions are smaller and given more frequently, often once or twice a week, and can usually be self-administered at home after proper training.
Managing CVID also involves other strategies. Prompt and aggressive use of antibiotics is necessary to treat any breakthrough bacterial infections that occur. Regular follow-up appointments with an immunologist are a standard part of care. These visits allow for monitoring of immunoglobulin levels, overall health status, and the early detection and management of any associated complications, such as autoimmune or lung conditions.