Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA.
[2] Symptoms generally include high susceptibility to pathogens, chronic lung disease, as well as inflammation and infection of the gastrointestinal tract.
[4] People with common variable immunodeficiency have trouble fighting off infections due to the lack of antibodies produced, which normally resist invading microbes.
Pathogens less often isolated from those affected include Neisseria meningitidis, Pseudomonas aeruginosa, respectively Giardia lamblia, Salmonella sp., Campylobacter jejuni for gastrointestinal tract.
Signs of a gastrovascular infection include abdominal pain, nausea, bloating, vomiting, diarrhea, and weight loss.
Many individuals with CVID have an impaired ability to absorb nutrients, including vitamins, proteins, minerals, fats, and sugar, within the digestive tract.
CVID patients with autoimmunity show decreased number of immunosuppressive regulatory T cells (Treg) and impaired selection process of self-reactive antibodies, suggesting the possible mechanism.
The heterogenous group of patients makes it difficult to find common grounds for treatment for the GI inflammation in CVID.
[7] Due to changes in B cell development, some individuals with CVID have accumulations of lymphocytes in lymphoid tissues.
Lymphocytic infiltration to tissues may cause enlargement of lymph nodes (lymphadenopathy), of the spleen (splenomegaly), and of the liver (hepatomegaly), as well as the formation of granulomas.
Several recent studies have described a potential role of epigenetics factor (including DNA methylation, chromatin and histone modulation and also non-coding RNAs) in pathogenesis of CVID.
There are also T cell abnormalities in CVID including counts, percentages, surface markers and function differences.
[21] As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if:[22] Diagnosis is chiefly by exclusion, i.e., alternative causes of hypogammaglobulinemia, such as X-linked agammaglobulinemia, must be excluded before a diagnosis of CVID can be made.
The following types of CVID have been identified, and correspond to mutations in different gene segments: Treatment options are limited and usually include lifelong immunoglobulin replacement therapy.
This treatment replenishes Ig subtypes that the person lacks, is given at frequent intervals for life, and is thought to help reduce bacterial infections and boost immune function.
[25] Before therapy begins, plasma donations are tested for known blood-borne pathogens, then pooled and processed to obtain concentrated IgG samples.
The administration of intravenous immunoglobulins requires the insertion of a cannula or needle in a vein, usually in the arms or hands.
Subcutaneous infusions slowly release the Ig serum underneath the skin, again through a needle, and take place every week.
People often experience adverse side effects from immunoglobulin infusions, including: In addition to Ig replacement therapy, treatment may also involve immune suppressants to control autoimmune symptoms of the disease and high-dose steroids like corticosteroids.
[28] The outlook for people varies greatly depending on their level of lung and other organ damage prior to diagnosis and treatment.
Current research is aimed at studying large cohorts of people with CVID in an attempt to better understand the age of onset as well as the mechanism, genetic factors, and progression of the disease.