Common variable immunodeficiency (CVID)

Antibodies, also called immunoglobulins, are proteins that mark germs so the immune system can destroy them. They are made by plasma cells, which grow from white blood cells called B cells. In CVID, people usually have normal numbers of B cells, but those cells do not mature properly into plasma cells, so the body makes too few antibodies.

Blood tests show a low level of IgG, often a low level of IgA and sometimes a low level of IgM. These are the three major types of antibody in the blood. Doctors also check how the body responds to vaccines such as tetanus or pneumococcal vaccines, because people with CVID make very few or no antibodies to most of them. Other causes of low antibodies, such as antibodies being lost through the gut or urine, have to be ruled out first.

It is called “common” because it is one of the most often diagnosed primary immunodeficiencies, a group of disorders of the immune system itself. It is called “variable” because antibody levels and the course of the illness differ a lot from person to person. CVID is not the same as the acquired immunodeficiency caused by HIV.

For about 9 in 10 people with CVID, the exact cause is not known. Experts think it usually comes from a mix of genetic and environmental factors that affect how B cells develop and work.

In about 1 in 10 people, a single gene change can be found, and changes in at least 13 genes have been linked to CVID. The most common involve a gene called TNFRSF13B. Even when a family shares a gene change, not everyone who inherits it develops CVID. Genetic testing is not needed for most people, but it can help guide treatment for people with autoimmune or inflammatory problems.

Most people with CVID have no family history of it. It is estimated to affect about 1 in 25,000 to 1 in 50,000 people worldwide, and the rate varies between populations. It affects both men and women.

Symptoms can begin at any age from childhood to adulthood. Most people are diagnosed in their 20s or 30s, but about 1 in 5 have symptoms or are found to have an immune problem as children. The most common sign is infections that keep coming back in the ears, sinuses, airways and lungs, including pneumonia. Repeated lung infections can scar and widen the airways, a lasting condition called bronchiectasis.

CVID can also turn the immune system against the body. About a quarter of people have an autoimmune problem, most often one that destroys platelets (immune thrombocytopenia) or red blood cells (autoimmune hemolytic anemia). For about 1 in 5 people, a very low platelet count or anemia is the first sign. Others develop diarrhea and weight loss, swollen lymph nodes, a large spleen, or small clusters of immune cells called granulomas in the lungs, liver or other organs.

People with CVID have a higher chance of some cancers, especially non-Hodgkin lymphoma, a cancer of immune cells, and less often stomach cancer. In a large group followed in New York, people who had complications beyond infection had about 11 times the risk of dying compared with those who did not. That is why care teams watch closely for these problems.

The main treatment is immunoglobulin replacement: antibodies made from donated plasma, pooled from thousands of screened donors. It can be given into a vein, usually every 3 to 4 weeks, or under the skin on a schedule that ranges from daily to every two weeks. The under-the-skin form is given at home by the person or a caregiver after training. For people without a major T-cell problem or organ damage, it almost always improves symptoms.

Antibiotics treat infections, and people with lasting sinus or lung disease may need them for long periods. Autoimmune, gut and inflammatory problems are usually treated with the same medicines used for anyone else, including newer biologic drugs, although they may respond less well in CVID. Regular checkups, at least once a year for people who are stable, watch blood counts, antibody levels, weight and lung function.

A donor (allogeneic) stem cell transplant replaces the blood-forming system, including the B cells, with a donor’s. It is not a standard treatment for CVID and has been used for only a small number of people with very serious complications, most often severe immune dysregulation, where the immune system attacks the body or causes harmful inflammation. In an international study of 25 people, the problem that led to transplant went away in most survivors, and half of the survivors could stop immunoglobulin. The authors advised it only for carefully selected people whose immune or genetic defect has been studied in depth.

Most people with CVID are able to carry out most, if not all, of their normal activities. Life usually includes regular immunoglobulin treatment, quick care for infections and ongoing visits with an immunologist. How well someone does depends partly on how much lung or other organ damage happened before diagnosis and treatment began.

Complications beyond infection, such as autoimmune disease, gut problems, granulomas or lymphoma, can have a big effect on quality of life and often need extra treatment. Some people with lung damage have CT scans of the chest every few years, and a lymph node that stays swollen may need a biopsy, although most turn out to be a harmless reaction.

Patient organizations run online groups where people with CVID and their families can meet others who understand life with the condition. The Immune Deficiency Foundation, for example, hosts a free virtual group just for people with CVID.

Most people with CVID will never need a stem cell donor. The treatment that supports them, immunoglobulin replacement, is made from plasma given by many healthy donors, which is a different kind of donation.

For the few people whose complications lead a team to consider a transplant, the donor search works as it does for other immune disorders. European transplant recommendations for adults with primary immunodeficiency list a matched brother or sister, a matched unrelated volunteer or a partly matched donor as options, each to be weighed case by case. They do not name CVID separately.

A matched unrelated volunteer from a registry can matter for that rare person with CVID, and for many others with blood and immune diseases. Joining a registry cannot promise a match for anyone, but more volunteers of every background widen the choices.