CVID prevalence is estimated to be in between 1:50,000 to 1:25,000, however in regions with a high rate of related marriage can increase to 1:10,000 to 1:5,000.

The most common cause is a failure in the development of certain white blood cells called B lymphocytes. These are the immune cells involved in antibody production. In other cases, defects in other immune cell types and non-immune organs have been described. In order for the body to defend itself from infectious agents, the different cells and components within the immune system need to be functional to bring about a proper immune response. A defect in any of these different components could ultimately cause a defective immune system.

The failure in the antibody production in CVID patients is believed to be caused by a combination of genetic and environmental factors. So far, in only a few cases of affected individuals has the genetic cause has been identified. Approximately 10% of the patients present a mutation in the TNFRSF13B (also known as TACI) gene, but the alteration of this gene does not fully determine the development of CVID given that there are family members of patients that are healthy even though they have the alteration. This underscores the multifactorial genetic and environmental component of this disease.

Mutations in at least 13 different genes that have been associated with the development of CVID in some individuals, highlighting the genetic heterogeneity of this condition. The most frequently observed genetic mutations occur in the TNFRSF13B gene, which encodes the protein Transmembrane Activator and CAML Interactor (TACI). TACI plays a crucial role in B cell activation and the switching of antibody classes. Other genes that have been implicated in CVID include CD19, CR2, ICOS, TNFRSF13C, NFKB1, NFKB2, CLTA4, PI3KCD, IKZF1, STAT3, CD81, CD20, CD2, and LRBA. These genes are involved in various critical aspects of immune cell development, signaling pathways, and overall function. Mutations in these CVID-associated genes often disrupt the normal development and function of B cells, ultimately leading to an inability to produce sufficient amounts of protective antibodies. The specific impact of each gene mutation can vary, contributing to the diverse clinical manifestations observed in CVID. These genetic variations can be inherited from parents in a subset of cases (around 10% where a genetic cause is identified) or can arise spontaneously as new mutations in the affected individual. Different modes of inheritance have been reported for CVID, including autosomal dominant inheritance with variable penetrance, autosomal recessive inheritance, and, less frequently, X-linked inheritance (see RareShare Guide on Genetic Inheritance).

While a genetic component is evident in some cases, environmental factors are also strongly suspected to play a role in the development of CVID, although the specific nature of these factors remains largely unclear. There is growing interest in the potential contribution of epigenetic changes, which are alterations in gene expression that do not involve changes to the underlying DNA sequence. These changes can be influenced by environmental exposures and lifestyle factors and are hypothesized to contribute to the development of CVID in some individuals.

Since CVID refers to a group of diseases, the symptoms and their severity differ from person to person. The severity and specific symptoms also vary among CVID patients within the same family. The onset of the symptoms also varies greatly, from the early childhood to the adulthood. Most patients do not present symptoms until their 20-40s.
The deficiency of antibodies leads to recurrent bacterial infections, especially in the respiratory tract. If these infections are not prevented or treated, a complication known as chronic lung disease (the irreversible damage of the lung tissue) can develop. Some individuals also present complications in the gastrointestinal tract due to infections or inflammation. This might provoke abdominal pain, bloating, nausea, diarrhea and weight loss.

The abnormal B lymphocyte maturation can induce an increased accumulation of these cells in the lymph nodes, liver or spleen, a condition known as lymphadenopathy, hepatomegaly or splenomegaly, respectively. 
People with CVID are more prone to develop certain types of cancer, especially lymphomas (uncontrolled proliferation of lymphocytes).

Some patients will present a complication known as an autoimmune disorder. In these disorders the immune cells recognize the healthy tissues of the body and mistakenly attack them as if they were foreign. That patients with CVID, without a fully functional immune system, are able to develop an autoimmune disorder is somewhat counterintuitive and not well understood.

The diagnosis is made by the presence of very low amounts of antibodies in the context of an unknown B-cell dysfunction; it is essentially a diagnosis by a process of elimination. Laboratory tests play a pivotal role in the diagnosis of CVID. Blood tests are essential for measuring the levels of the key immunoglobulin classes: IgG, IgA, and IgM. An analysis of B cell numbers is also helpful and is performed using flow cytometry, a technique that allows for the identification and quantification of different B cell subsets. Assessing an individual's antibody response to vaccination can be another component of the diagnostic workup for CVID. Genetic testing may be  particularly relevant in cases with an early age of disease onset, the presence of autoimmune or inflammatory complications, a family history suggestive of an inherited antibody deficiency, or when there is a need to exclude other primary immunodeficiencies that have known genetic causes.

There is not a single test to determine if a person has CVID, the diagnosis is made after a thorough examination. When a person presents the characteristic symptoms, the first step is to confirm a lower amount of antibodies than age specific normal range in a blood test. 

The primary therapy for CVID patients is immunoglobulin replacement therapy, which consists of the regular administration of antibodies either intravenously or subcutaneously. Immunoglobulin is another word for the antibody. This therapy replaces the missing antibodies and can help to prevent recurrent infections, but only mildly helps with non-infectious symptoms of the disease. If this therapy is ineffective in controlling infections, antibiotics can be prescribed to treat certain infections as they appear. Other complications can be treated as they arise, such as in the case of severe autoimmune disease, where steroids or other immuosuppressive drugs can be administered.
 

The prognosis for individuals diagnosed with Common Variable Immunodeficiency is influenced by a variety of factors, including the severity and frequency of the illnesses they experience. Several factors have been identified as potentially impacting the long-term outlook for individuals with CVID. Older age at the time of diagnosis, lower baseline levels of IgG antibodies, higher levels of IgM antibodies, and a reduced number of peripheral B cells have been associated with poorer survival rates. The presence of non-infectious complications, such as lymphoma, hepatitis, functional or structural lung impairment, and gastrointestinal disease, has also been linked to reduced survival. Specifically, complications like structural lung damage, including bronchiectasis or granulomas, chronic hepatitis, lymphoma, and chronic gastrointestinal diseases, can negatively affect the overall prognosis.

Despite these potential complications, the advent of immunoglobulin replacement therapy has significantly improved the life expectancy for individuals with CVID. Studies indicate that the majority of individuals with CVID (over 75%) are alive 25 years after their diagnosis, and approximately half live for 45 years or more. Recent research suggests that individuals with CVID who only experience recurrent infections may have a near-normal life expectancy post-diagnosis. Lung disease remains the most common cause of death in individuals with CVID 29. With consistent treatment and appropriate management, many individuals with CVID can lead active and fulfilling lives.
 

1. http://emedicine.medscape.com/article/1051103
2. https://rarediseases.org/rare-diseases/common-variable-immune-deficiency
3. https://rarediseases.info.nih.gov/diseases/6140/common-variable-immunodeficiency
4. Kienzler, A. K., et al. (2017). "The role of genomics in common variable immunodeficiency disorders." Clin Exp Immunol 188(3): 326-332.
5. Verywell Health:  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552.