Common variable immunodeficiency (CVID) is characterized by low levels of antibodies and an increased risk of infections. Although the disease usually is diagnosed in adults, it also can occur in children. CVID also is known as hypogammaglobulinemia, adult-onset agammaglobulinemia, late-onset hypogammaglobulinemia, and acquired agammaglobulinemia.

NIAID supports research to determine genetic causes of CVID that may lead to therapeutic approaches to address the disease. Researchers also are exploring how antibody-based drugs may lessen the severity of the condition. CVID is a primary immune deficiency disease (PIDD).

Causes

CVID is caused by a variety of different genetic abnormalities that result in a defect in the capability of immune cells to produce normal amounts of all types of antibodies. Only a few of these defects have been identified, and the cause of most cases of CVID is unknown. Many people with CVID carry a DNA variation called a polymorphism in a gene known as TACI. However, while this genetic abnormality confers increased risk of developing CVID, it alone is not capable of causing CVID.

IgA deficiency is a related condition in which only the level of the antibody immunoglobulin A (IgA) is low, while levels of other antibody types such as IgG and IgM are usually normal or near normal. IgA deficiency typically occurs alone, but in some cases it may precede the development of CVID or occur in family members of CVID patients.

Symptoms & Diagnosis

People with CVID may experience frequent bacterial and viral infections of the upper airway, sinuses, and lungs. Acute lung infections can cause pneumonia, and long-term lung infections may cause a chronic form of bronchitis known as bronchiectasis, which is characterized by thickened airway walls colonized by bacteria.

People with CVID also may have diarrhea, problems absorbing food nutrients, reduced liver function, and impaired blood flow to the liver. Autoimmune problems that cause reduced levels of blood cells or platelets also may occur. People with CVID may develop an enlarged spleen and swollen glands or lymph nodes. Painful swollen joints in the knee, ankle, elbow, or wrist also can develop. In addition, people with CVID may have an increased risk of developing some cancers.

Doctors can diagnose CVID by weighing factors including infection history, digestive symptoms, lab tests showing very low immunoglobulin levels, and low antibody responses to immunization.

Treatment

CVID is treated with intravenous immunoglobulin infusions or subcutaneous (under the skin) immunoglobulin injection to partially restore immunoglobulin levels. The immunoglobulin given by either method provides antibodies from the blood of healthy donors. The frequent bacterial infections experienced by people with CVID are treated with antibiotics. Other problems caused by CVID may require additional, tailored treatments.

The symptoms of common variable immunodeficiency (CVID) may be different from person to person. Some people may be more severely affected than others, even people who have the same form. Not everyone with common variable immunodeficiency will have the same symptoms.

The most common signs and symptoms of CVID include :

• Low levels of proteins that help the immune system work (immunoglobulins)
• Recurrent infections especially of the lungs and digestive systems
• Autoimmunity (body attacks healthy organs and tissues)
• Liver involvement
• Increased risk for malignancy

About 20-30% of people with CVID will develop autoimmunity, and about 10% of people with CVID will have liver involvement.

The main treatment for common variable immunodeficiency (CVID) is Ig replacement therapy, which stops the cycle of recurrent infections. Ig may be taken intravenously (through the vein) or subcutaneously (by injection). Adverse reactions to Ig must be monitored during therapy. In some people with CVID and severe autoimmune disease, steroids or other immunosuppressive drugs in addition to Ig therapy may be needed.

There are multiple forms of Ig replacement therapy available and people with CVID should speak to their health care providers to determine which therapy may be best for their situation.

There are risks associated with pregnancy in women with CVID. However, with appropriate medical management and surveillance, women with CVID can have a pregnancy without increased risk of infection, and a baby born with adequate IgG levels. We are not aware of an increased risk of infertility (being unable to conceive) being directly associated with having CVID. However, women with CVID may be at increased risk for miscarriage.

An infant's immune system is immature at birth, and during the first few months of life. Transport of IgG through the placenta (which occurs mainly after 32 weeks gestation) plays a central role in protecting the infant from infections. Having regular IgG replacement therapy is crucial both during pregnancy and during the first few weeks after childbirth. This therapy is needed for the mother's health, and for the baby's health (it provides immunological protection for the infant). Without therapy during pregnancy, fetuses and newborns may have an increased risk of infection.

Stable, protective IgG levels are reached only after 3–6 months of replacement therapy. Therefore, IgG treatment should be started by the early stages of pregnancy to ensure stable levels in both the mother and the infant. Several case reports of pregnant women with CVID have indicated a need to increase the dosage of IgG throughout pregnancy to maintain adequate levels. Pregnant women with CVID should be regularly monitored (by both their immunologist and obstetrician), and adjustments to doses may be needed to prevent pregnancy-associated infections or potential complications. Stable IgG levels in the mother avoids having to infuse IgG in the infant. Another protective factor for the infant is breastfeeding.

Newborns of mothers with CVID should have serum IgG tested and be closely observed for infections. If IgG levels in the newborn are not high enough, IgG replacement therapy or donor breast milk supplements can be used depending on the severity of the IgG deficiency in the newborn.

To our knowledge, there is limited information about breastfeeding in women with CVID who have been on Ig therapy during and/or after pregnancy.

While immune globulins from Ig therapy may be present in breast milk, measurements of concentrations (taken from only two lactating mothers on therapy) did not produce significant or consistent findings. However, immune globulins are normal components of human milk.

In 2009, researchers published a report about two mothers with CVID and their infants. During pregnancy both women continued intravenous Ig (IVIG) therapy. The authors concluded that breastfeeding should be encouraged, as colostrum from these women provided immunological protection, plus nutritional and psychological benefits for the infant.

IVIG is considered a therapeutic option for mothers with multiple sclerosis (MS) who are breastfeeding. A study that included 69 women with MS who had received IVIG postpartum did not include any reports of serious adverse effects among the exposed nursing infants.In another case series of 43 women with MS who received 60 g IVIG within 3 days postpartum, and 10 g/month thereafter, there was only a transient rash one day after a mother's dose. The rash might have been from the IVIG. All women breastfed for at least 4 weeks.

We are unable to make recommendations about whether to breastfeed or formula feed, as this is a personal decision. While many health organizations recommend breastfeeding in general, breastfeeding may not be possible for all women, especially in specific medical situations. For mothers who are unable to breastfeed or decide not to, formula is a healthy alternative and provides infants with the nutrients they need.

Women with CVID and on Ig therapy who have questions or concerns about breastfeeding are encouraged to speak with their immunologist for information and/or advice.