Common variable immune deficiency

Description

Common variable immune deficiency (CVID) is a disorder that impairs the immune
system. People with CVID are highly susceptible to infection from foreign invaders such
as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in
the lungs, sinuses, and ears. Pneumonia is common in people with CVID. Over time,
recurrent infections can lead to chronic lung disease. Affected individuals may also
experience infection or inflammation of the gastrointestinal tract, which can cause
diarrhea and weight loss. Abnormal accumulation of immune cells causes enlarged
lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly) in some people
with CVID. Immune cells can accumulate in other organs, forming small lumps called
granulomas.

Approximately 25 percent of people with CVID have an autoimmune disorder, which

occurs when the immune system malfunctions and attacks the body's tissues and
organs. The blood cells are most frequently affected by autoimmune attacks in CVID;
the most commonly occurring autoimmune disorders are immune thrombocytopenia,
which is an abnormal bleeding disorder caused by a decrease in cells involved in blood
clotting called platelets, and autoimmune hemolytic anemia, which results in premature
destruction of red blood cells. Other autoimmune disorders such as rheumatoid arthritis
can occur. Individuals with CVID also have a greater than normal risk of developing
certain types of cancer, including a cancer of immune system cells called non-Hodgkin
lymphoma and less frequently, stomach (gastric) cancer.

People with CVID may start experiencing signs and symptoms of the disorder anytime
between childhood and adulthood; most people with CVID are diagnosed in their
twenties or thirties. The life expectancy of individuals with CVID varies depending on the
severity and frequency of illnesses they experience. Most people with CVID live into
adulthood.

There are many different types of CVID that are distinguished by genetic cause. People
with the same type of CVID may have varying signs and symptoms.

Frequency

CVID is estimated to affect 1 in 25,000 to 1 in 50,000 people worldwide, although the

prevalence can vary across different populations.

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1

Causes
The cause in CVID is unknown in approximately 90 percent of cases. It is likely that this
condition is caused by both environmental and genetic factors. While the specific
environmental factors are unclear, the genetic influences in CVID are believed to be
mutations in genes that are involved in the development and function of immune system
cells called B cells. B cells are specialized white blood cells that help protect the body
against infection. When B cells mature, they produce special proteins called antibodies (
also known as immunoglobulins). These proteins attach to foreign particles, marking
them for destruction. Mutations in the genes associated with CVID result in
dysfunctional B cells that cannot make sufficient amounts of antibodies.

In about 10 percent of cases, a genetic cause for CVID is known. Mutations in at least
13 genes have been associated with CVID. The most frequent mutations occur in the
TNFRSF13B gene. The protein produced from this gene plays a role in the survival and
maturation of B cells and in the production of antibodies. TNFRSF13B gene mutations
disrupt B cell function and antibody production, leading to immune dysfunction. Other
genes associated with CVID are also involved in the function and maturation of immune
system cells, particularly of B cells; mutations in these genes account for only a small
percentage of cases.

All individuals with CVID have a shortage (deficiency) of two or three specific antibodies.
Some have a deficiency of the antibodies called immunoglobulin G (IgG) and
immunoglobulin A (IgA), while others, in addition to lacking IgG and IgA, are also
deficient in immunoglobulin M (IgM). A shortage of these antibodies makes it difficult for
people with this disorder to fight off infections. Abnormal and deficient immune
responses over time likely contribute to the increased cancer risk. In addition, vaccines
for diseases such as measles and influenza do not provide protection for people with
CVID because they cannot produce an antibody response.

Learn more about the gene associated with Common variable immune deficiency
• TNFRSF13B

Additional Information from NCBI Gene:

• CD19
• CD81
• CR2
• ICOS
• IKZF1
• IL21
• LRBA
• MS4A1
• NFKB1

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2

• NFKB2
• PRKCD
• TNFRSF13C

Inheritance

Most cases of CVID are sporadic and occur in people with no apparent history of the
disorder in their family. These cases probably result from a complex interaction of
environmental and genetic factors.

In rare cases, CVID is inherited in an autosomal recessive pattern, which means both
copies of a gene in each cell have mutations. The parents of an individual with an
autosomal recessive condition each carry one copy of the mutated gene, but they
typically do not show signs and symptoms of the condition.

In a few cases, this condition is inherited in an autosomal dominant pattern, which

means one copy of an altered gene in each cell is sufficient to cause the disorder.

When CVID is caused by mutations in the TNFRSF13B gene, it is often sporadic and
the result of a new mutation in the gene that occurs during the formation of reproductive
cells (eggs or sperm) or in early embryonic development. When TNFRSF13B gene
mutations are inherited, they can cause either autosomal dominant CVID or autosomal
recessive CVID.

Not all individuals who inherit a gene mutation associated with CVID will develop the
disease. In many cases, affected children have an unaffected parent who has the same
mutation. Additional genetic or environmental factors are likely needed for the disorder
to occur.

Other Names for This Condition

• Common variable hypogammaglobulinemia
• Common variable immunodeficiency
• CVID
• Immunodeficiency, common variable

Additional Information & Resources

Genetic Testing Information

• Genetic Testing Registry: Common variable immunodeficiency (https://www.ncbi.nl

m.nih.gov/gtr/conditions/C0009447/)

Genetic and Rare Diseases Information Center

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3

• Common variable immunodeficiency (https://rarediseases.info.nih.gov/diseases/614
0/index)

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD) (https://rarediseases.org/)

Clinical Trials
• ClinicalTrials.gov (https://clinicaltrials.gov/search?cond=%22Common variable imm
une deficiency%22)

Catalog of Genes and Diseases from OMIM

• IMMUNODEFICIENCY, COMMON VARIABLE, 2; CVID2 (https://omim.org/entry/24
0500)
• IMMUNODEFICIENCY, COMMON VARIABLE, 1; CVID1 (https://omim.org/entry/60
7594)
• AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE III; ALPS3 (https://
omim.org/entry/615559)
• IMMUNODEFICIENCY, COMMON VARIABLE, 10; CVID10 (https://omim.org/entry/
615577)
• IMMUNODEFICIENCY, COMMON VARIABLE, 3; CVID3 (https://omim.org/entry/61
3493)
• IMMUNODEFICIENCY, COMMON VARIABLE, 4; CVID4 (https://omim.org/entry/61
3494)
• IMMUNODEFICIENCY, COMMON VARIABLE, 5; CVID5 (https://omim.org/entry/61
3495)
• IMMUNODEFICIENCY, COMMON VARIABLE, 6; CVID6 (https://omim.org/entry/61
3496)
• IMMUNODEFICIENCY, COMMON VARIABLE, 13; CVID13 (https://omim.org/entry/
616873)
• IMMUNODEFICIENCY, COMMON VARIABLE, 7; CVID7 (https://omim.org/entry/61
4699)
• IMMUNODEFICIENCY, COMMON VARIABLE, 8, WITH AUTOIMMUNITY; CVID8 (
https://omim.org/entry/614700)
• IMMUNODEFICIENCY, COMMON VARIABLE, 11; CVID11 (https://omim.org/entry/
615767)
• IMMUNODEFICIENCY, COMMON VARIABLE, 12, WITH AUTOIMMUNITY;
CVID12 (https://omim.org/entry/616576)

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 4

Scientific Articles on PubMed
• PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28%28common+variable+immu
ne+deficiency%5BTI%5D%29+OR+%28CVID%5BTI%5D%29%29+AND+english%5
Bla%5D+AND+human%5Bmh%5D+AND+%22last+3600+days%22%5Bdp%5D)

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Last updated May 1, 2016

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 6