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Common variable immune deficiency

Reviewed March 2010

What is common variable immune deficiency?

Common variable immune deficiency (CVID) is a disorder that damages the immune system. Because their immune system cannot adequately protect them, people with CVID can develop recurrent infections in the lungs, sinuses, or ears. Over time, recurrent lung infections can lead to chronic lung disease and life-threatening breathing problems. Most people with CVID also have pneumonia at least once in their life. Affected individuals may also experience gastrointestinal problems, such as infections or inflammation. These problems can cause bloating, diarrhea, decreased absorption of nutrients, and weight loss. For reasons that are unclear, some people with CVID have enlarged lymph nodes or an enlarged spleen (splenomegaly).

Approximately 20 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 autoimmune disorder most commonly seen in people with CVID is immune thrombocytopenia purpura. This condition is characterized by a reduced number of platelets in the blood, which leads to abnormal bruising and bleeding. Individuals with CVID also have a somewhat higher than normal risk of developing certain types of cancer, including cancer of immune system cells called non-Hodgkin lymphoma. Some studies have found an increased risk of developing stomach cancer in people with CVID.

People with CVID may start experiencing signs and symptoms of the disorder in childhood or adolescence, but the majority of affected individuals do not experience immune problems related to CVID until adulthood.

How common is common variable immune deficiency?

The exact prevalence of CVID is unknown. It is estimated to affect 1 in 25,000 to 1 in 50,000 people.

What genes are related to common variable immune deficiency?

CVID is believed to result from mutations in genes that are involved in the development and function of 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 (which are also known as immunoglobulins). These proteins attach to specific foreign particles and germs, marking them for destruction. Mutations in the genes associated with CVID result in dysfunctional B cells that cannot make sufficient amounts of antibodies.

People with CVID have a shortage (deficiency) of specific proteins called immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM). The lack of certain antibodies makes it difficult for people with this disorder to fight off infections. In addition, vaccines do not provide protection for people with CVID because these individuals lack antibodies.

Mutations in at least five genes have been associated with CVID. Approximately 10 percent of affected individuals have mutations in the TNFRSF13B gene. Mutations in each of the other genes associated with CVID account for only a small percentage of cases.

In most cases of CVID, the cause is unknown.

Related Gene(s)

Changes in these genes are associated with common variable immune deficiency.

  • CD19
  • CD81
  • ICOS
  • TNFRSF13B
  • TNFRSF13C

How do people inherit common variable immune deficiency?

Most cases of CVID are classified as sporadic and occur in people with no apparent history of the disorder in their family. Although the cause of these cases is unclear, sporadic cases probably result from a complex interaction of environmental and genetic factors.

In a few families, CVID is inherited in an autosomal recessive pattern, which means both copies of the 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 very rare cases, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

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 shares the same mutation.

Where can I find information about diagnosis or management of common variable immune deficiency?

These resources address the diagnosis or management of common variable immune deficiency and may include treatment providers.

  • Gene Review: Common Variable Immune Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1299/)
  • Genetic Testing Registry: Common variable agammaglobulinemia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0009447)
  • Genetic Testing Registry: Immunodeficiency, common variable, 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150740)
  • Genetic Testing Registry: Immunodeficiency, common variable, 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150741)
  • Genetic Testing Registry: IMMUNODEFICIENCY, COMMON VARIABLE, 8, WITH AUTOIMMUNITY (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN130276)
  • National Marrow Donor Program: Inherited Immune System Disorders (http://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/Immune_System/Inherited_Immune_System_Disorders.aspx)
  • United States Immunodeficiency Network (http://www.usidnet.org/)

You might also find information on the diagnosis or management of common variable immune deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/common-variable-immune-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/common-variable-immune-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about common variable immune deficiency?

You may find the following resources about common variable immune deficiency helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    Health Topic: Immune System and Disorders (http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6140/resources/resources/1)
  • Additional NIH Resources - National Institutes of Health
    Eunice Kennedy Shriver National Institute of Child Health and Human Development: Primary Immunodeficiency (http://www.nichd.nih.gov/publications/pubs/Pages/primary_immuno.aspx)

  • Educational resources - Information pages

    • Children's Hospital Boston: Immune System (http://www.childrenshospital.org/az/Site2177/mainpageS2177P0.html)
    • Immune Deficiency Foundation: Common Variable Immune Deficiency (http://primaryimmune.org/about-primary-immunodeficiency-diseases/types-of-pidd/common-variable-immune-deficiency)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=125)
    • Merck Manual Home Edition for Patients and Caregivers (http://www.merckmanuals.com/home/immune_disorders/immunodeficiency_disorders/common_variable_immunodeficiency.html)
    • The Swedish Information Centre for Rare Diseases (http://www.socialstyrelsen.se/rarediseases/commonvariableimmunodeficiency)
    • United States Immunodeficiency Network (http://www.usidnet.org/)

  • Patient support - For patients and families

    • Family Village: Immune Deficiencies and Disorders (http://www.familyvillage.wisc.edu/lib_immu.htm)
    • Immune Deficiency Foundation (http://primaryimmune.org/)
    • National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/807/viewAbstract)
    • Primary Immunodeficiency Resource Center (http://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=syndromes&area=4&CFID=32813331&CFTOKEN=3862055)
    • University of Kansas Medical Center Resource List: Immune Deficiency Conditions (http://www.kumc.edu/gec/support/immune.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1299/)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Common variable agammaglobulinemia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0009447)
    • Genetic Testing Registry: Immunodeficiency, common variable, 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150740)
    • Genetic Testing Registry: Immunodeficiency, common variable, 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150741)
    • Genetic Testing Registry: IMMUNODEFICIENCY, COMMON VARIABLE, 8, WITH AUTOIMMUNITY (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN130276)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Common%20Variable%20Immunodeficiency%22%20OR%20%22common%20variable%20immune%20deficiency%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((common%20variable%20immune%20deficiency%5BTI%5D)%20OR%20(CVID%5BTI%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/240500)

What other names do people use for common variable immune deficiency?

  • common variable agammaglobulinemia
  • common variable hypogammaglobulinemia
  • common variable immunodeficiency
  • immunodeficiency, common variable

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about common variable immune deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding common variable immune deficiency?

autoimmune ; autosomal ; autosomal dominant ; autosomal recessive ; cancer ; cell ; chronic ; deficiency ; enlarged spleen ; gastrointestinal ; gene ; immune system ; immunodeficiency ; immunoglobulin ; infection ; inflammation ; lymph ; lymphoma ; mutation ; platelets ; pneumonia ; prevalence ; purpura ; recessive ; splenomegaly ; sporadic ; stomach ; thrombocytopenia ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bacchelli C, Buckridge S, Thrasher AJ, Gaspar HB. Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol. 2007 Sep;149(3):401-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17697196?dopt=Abstract)
  • Cunningham-Rundles C, Knight AK. Common variable immune deficiency: reviews, continued puzzles, and a new registry. Immunol Res. 2007;38(1-3):78-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17917013?dopt=Abstract)
  • Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008 May;28 Suppl 1:S42-5. doi: 10.1007/s10875-008-9182-7. Epub 2008 Mar 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18322785?dopt=Abstract)
  • Deane S, Selmi C, Naguwa SM, Teuber SS, Gershwin ME. Common variable immunodeficiency: etiological and treatment issues. Int Arch Allergy Immunol. 2009;150(4):311-24. doi: 10.1159/000226232. Epub 2009 Jul 1. Review. Erratum in: Int Arch Allergy Immunol. 2010;151(4):284. Dosage error in article text. (http://www.ncbi.nlm.nih.gov/pubmed/19571563?dopt=Abstract)
  • Poodt AE, Driessen GJ, de Klein A, van Dongen JJ, van der Burg M, de Vries E. TACI mutations and disease susceptibility in patients with common variable immunodeficiency. Clin Exp Immunol. 2009 Apr;156(1):35-9. doi: 10.1111/j.1365-2249.2008.03863.x. Epub 2008 Dec 11. (http://www.ncbi.nlm.nih.gov/pubmed/19210517?dopt=Abstract)
  • Schäffer AA, Salzer U, Hammarström L, Grimbacher B. Deconstructing common variable immunodeficiency by genetic analysis. Curr Opin Genet Dev. 2007 Jun;17(3):201-12. Epub 2007 Apr 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17467261?dopt=Abstract)
  • van de Ven AA, van de Corput L, van Tilburg CM, Tesselaar K, van Gent R, Sanders EA, Boes M, Bloem AC, van Montfrans JM. Lymphocyte characteristics in children with common variable immunodeficiency. Clin Immunol. 2010 Apr;135(1):63-71. doi: 10.1016/j.clim.2009.11.010. Epub 2009 Dec 16. (http://www.ncbi.nlm.nih.gov/pubmed/20006554?dopt=Abstract)
  • van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010 Apr;120(4):1265-74. doi: 10.1172/JCI39748. Epub 2010 Mar 8. (http://www.ncbi.nlm.nih.gov/pubmed/20237408?dopt=Abstract)
  • Yong PF, Tarzi M, Chua I, Grimbacher B, Chee R. Common variable immunodeficiency: an update on etiology and management. Immunol Allergy Clin North Am. 2008 May;28(2):367-86, ix-x. doi: 10.1016/j.iac.2008.01.001. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18424338?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2010
Published: May 20, 2013