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| | {{Short description|A primary immunodeficiency disorder}} |
| {{Infobox medical condition (new) | | {{Infobox medical condition (new) |
| | name = Common variable immunodeficiency | | | name = Common variable immunodeficiency |
| | synonyms = | | | synonyms = CVID, Acquired hypogammaglobulinemia |
| | image =
| | | field = [[Immunology]] |
| | caption =
| | | symptoms = Recurrent respiratory and gastrointestinal infections, fatigue, autoimmune disorders, enlarged lymph nodes, splenomegaly |
| | pronounce =
| | | complications = Chronic lung disease, lymphoma, autoimmune diseases, gastrointestinal inflammation |
| | field = | | | onset = Usually in late childhood or early adulthood (ages 20–40) |
| | symptoms = | | | duration = Lifelong |
| | complications = | | | types = Varies depending on severity and complications |
| | onset = | | | causes = Mostly unknown; associated with genetic mutations in some cases (e.g., TNFRSF13B, ICOS) |
| | duration = | | | risks = Family history of immunodeficiency, autoimmune disorders |
| | types = | | | diagnosis = Low levels of immunoglobulins (especially IgG, IgA, and/or IgM), poor response to vaccines, clinical symptoms |
| | causes = | | | differential = [[X-linked agammaglobulinemia]], [[Selective IgA deficiency]], [[Hyper IgM syndrome]] |
| | risks = | | | prevention = None |
| | diagnosis = | | | treatment = Immunoglobulin replacement therapy (IVIG or SCIG), treatment of infections, immunosuppressants for autoimmune complications |
| | differential = | | | medication = Immunoglobulin therapy, antibiotics, corticosteroids, immunomodulators |
| | prevention = | | | prognosis = Variable; improved with treatment, but increased risk of complications |
| | treatment = | | | frequency = Estimated at 1 in 25,000 to 1 in 50,000 people |
| | medication = | | | deaths = Related to complications if untreated or misdiagnosed |
| | prognosis = | |
| | frequency = | |
| | deaths = | |
| }} | | }} |
| <!-- Definition and symptoms -->
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| '''Common variable immunodeficiency''' ('''CVID''') is an [[immune disorder]] characterized by recurrent infections and low [[antibody]] levels, specifically in [[immunoglobulin]] (Ig) types IgG, IgM and IgA.<ref name="CVID Lib of Medicine">{{cite web|title=Common Variable Immune Deficiency|url=http://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency|website=Genetics Home Reference|accessdate=8 February 2016}}</ref> Generally symptoms include high susceptibility to foreign invaders, [[chronic lung disease (disambiguation)|chronic lung disease]], and inflammation and infection of the gastrointestinal tract.<ref name="CVID Lib of Medicine" /> However, symptoms vary greatly between people. "Variable" refers to the heterogeneous clinical manifestations of this disorder, which include recurrent bacterial infections, increased risk for autoimmune disease and lymphoma, as well as gastrointestinal disease.<ref name="UpToDate: CVID in adults">Cunningham-Rundles, C. Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults. In: UpToDate, Notarangelo, LD, Feldweg, AM (Eds), UpToDate, Waltham, MA, 2020. Retrieved April 08, 2020.</ref> CVID is a lifelong disease.
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| <!-- Cause and diagnosis -->
| | '''Common variable immunodeficiency''' (CVID) is a primary immunodeficiency disorder characterized by low levels of serum immunoglobulins and an increased susceptibility to infections. It is one of the most frequently diagnosed primary immunodeficiencies and can present at any age, although it is most commonly diagnosed in adults. |
| The cause of CVID is poorly understood. Deletions in genes that encode cell surface proteins and cytokine receptors, such as [[CD19]], [[CD20]], [[CD21]], and [[CD80]], is a likely cause.<ref name="CVID diagnosis" /> A [[Deletion (genetics)|deletion]] is a mutation in which part of the chromosome is lost during DNA replication which may include several genes, or as few as a single base pair. Additionally, the disease is defined by [[T cell]] defects, namely reduced proliferative capacity.<ref name="CVID">{{cite journal|last1=Strober|first1=Warren|last2=Chua|first2=Kevin|title=Common Variable Immunodeficiency|journal=Clinical Reviews in Allergy and Immunology|date=2000|volume=19|issue=2|pages=157–181|doi=10.1385/criai:19:2:157|pmid=11107500|url=https://zenodo.org/record/1236299}}</ref> The disease is hard to diagnose, taking on average 6–7 years after onset.<ref name="CVID diagnosis" />
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| <ref name="many faces of CVID">{{cite journal|last1=Resnick|first1=Elena S.|last2=Cunningham-Rundles|first2=Charlotte|title=The many faces of the clinical picture of common variable immune deficiency|journal=Current Opinion|date=2012|volume=12|issue=6|pages=595–601|doi=10.1097/aci.0b013e32835914b9|pmid=23026770}}</ref> CVID is a [[primary immunodeficiency]].<ref name="CVID diagnosis">{{cite journal|last1=Abbott|first1=Jordan K.|last2=Gelfand|first2=Erwin W.|title=Common Variable Immunodeficiency: Diagnosis, Management, and Treatment|journal=Immunol Allergy Clin N Am|date=2015|volume=35|issue=4|pages=637–658|doi=10.1016/j.iac.2015.07.009|pmid=26454311}}</ref>
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| <!-- Treatment -->
| | ==Pathophysiology== |
| Treatment options are limited, and usually include lifelong [[immunoglobulin]] replacement therapy.<ref name="many faces of CVID" /> This therapy is thought to help reduce bacterial infections. This treatment alone is not wholly effective, and many people still experience other symptoms like lung disease and noninfectious inflammatory symptoms.
| | CVID is a heterogeneous disorder with a complex pathophysiology. It involves defects in the [[B cell]] differentiation process, leading to impaired production of [[immunoglobulins]] (antibodies). This results in decreased levels of [[IgG]], [[IgA]], and sometimes [[IgM]]. The exact genetic causes of CVID are not fully understood, but mutations in several genes, including [[TNFRSF13B]] (TACI), have been implicated. |
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| <!-- History and epidemiology -->
| | ==Clinical Features== |
| CVID was first diagnosed over 60 years ago, and since has emerged as the predominant class of primary antibody deficiencies. CVID is formally diagnosed by levels of IgG and IgA more than two standard deviations below the norm, and no other cause for [[hypogammaglobulinemia]], an abnormally low level of immunoglobulins in the blood. It is thought to affect between 1 in 25,000 to 1 in 50,000 people worldwide. | | Patients with CVID typically present with recurrent infections, particularly of the [[respiratory tract]], such as [[sinusitis]], [[bronchitis]], and [[pneumonia]]. They may also experience gastrointestinal infections and chronic diarrhea. In addition to infections, individuals with CVID are at increased risk for autoimmune disorders, [[granulomatous disease]], and certain types of [[cancer]], particularly [[lymphoma]]. |
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| == Signs and symptoms == | | ==Diagnosis== |
| | The diagnosis of CVID is based on clinical presentation and laboratory findings. Key diagnostic criteria include: |
| | * Low levels of serum [[IgG]], [[IgA]], and/or [[IgM]] |
| | * Poor response to vaccines |
| | * Exclusion of other causes of hypogammaglobulinemia |
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| The symptoms of CVID vary between people affected. Its main features are [[hypogammaglobulinemia]] and recurrent infections. Hypogammaglobulinemia manifests as a significant decrease in the levels of [[IgG]] antibodies, usually alongside [[IgA]] antibodies; [[IgM]] antibody levels are also decreased in about half of people.<ref name=Herriot2008>{{cite journal |vauthors=Herriot R, Sewell WA |title=Antibody deficiency |journal=Journal of Clinical Pathology |volume=61 |issue=9 |pages=994–1000 |year=2008 |pmid=18755724 |doi=10.1136/jcp.2007.051177 |url=}}</ref> Infections are a direct result of the low antibody levels in the circulation, which do not adequately protect them against pathogens. The microorganisms that most frequently cause infections in CVID are bacteria [[Haemophilus influenzae]], [[Streptococcus pneumoniae]] and [[Staphylococcus aureus]]. Pathogens less often isolated from people include [[Neisseria meningitidis]], [[Pseudomonas aeruginosa]] and [[Giardia lamblia]]. Infections mostly affect the respiratory tract (nose, sinuses, bronchi, lungs) and the ears; they can also occur at other sites, such as the eyes, skin and gastrointestinal tract. These infections respond to antibiotics but can recur upon discontinuation of antibiotics. [[Bronchiectasis]] can develop when severe, recurrent pulmonary infections are left untreated.
| | Additional tests may include assessment of B cell numbers and function, as well as genetic testing to identify potential mutations associated with the disorder. |
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| In addition to infections, people with CVID can develop complications. These include:
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| * autoimmune manifestations, e.g. [[pernicious anemia]], [[autoimmune haemolytic anemia]] (AHA), [[idiopathic thrombocytopenic purpura]] (ITP), [[psoriasis]], [[vitiligo]], [[rheumatoid arthritis]], primary [[hypothyroidism]], [[atrophic gastritis]]. Autoimmunity is the main type of complication in people with CVID, appearing in some form in up to 50% of individuals;
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| * malignancies, particularly [[Non-Hodgkin's lymphoma]] and [[gastric carcinoma]];
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| * enteropathy, which manifests with a blunting of [[intestinal villi]] and inflammation, and is usually accompanied by symptoms such as abdominal cramps, diarrhea, constipation and, in some cases, malabsorption and weight loss. Symptoms of CVID enteropathy are similar to those of [[celiac disease]], but don't respond to a gluten-free diet. Infectious causes must be excluded before a diagnosis of enteropathy can be made, as people with CVID are more susceptible to intestinal infections, e.g. by [[Giardia lamblia]];
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| * lymphocytic infiltration of tissues, which can cause enlargement of lymph nodes ([[lymphadenopathy]]), of the spleen ([[splenomegaly]]) and of the liver ([[hepatomegaly]]), as well as the formation of [[granulomas]]. In the lung this is known as [[Granulomatous–lymphocytic interstitial lung disease]].
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| Anxiety and depression can occur as a result of dealing with the other symptoms.<ref>Sanger, David E. [http://www.pia.org.uk/psychosocialstudysummary.htm "An Investigation of Coping and Psychosocial Functioning in Persons with Common Variable Immunodeficiency (CVID)"] {{Webarchive|url=https://archive.is/20030728061640/http://www.pia.org.uk/psychosocialstudysummary.htm |date=2003-07-28 }}, ''Barts and The London NHS Trust'', 2003, accessed August 7, 2011.</ref>
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| CVID patients generally complain of severe fatigue.<ref>{{cite web|url=https://www.patientslikeme.com/symptoms/show/7-fatigue?condition_id=673|title=PatientsLikeMe - Symptoms|author=|date=|website=www.patientslikeme.com|accessdate=14 April 2018}}</ref>
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| ==Causes==
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| The underlying causes of CVID are largely obscure.<ref name="many faces of CVID" /> Genetic mutations can be identified as the cause of disease in about 10% of people, while familial inheritance accounts for 10-25% of cases.<ref name="CVID new look at old disease" /> Rather than arising from a single genetic mutation, CVID seems to result from variety of mutations that all contribute to a failure in [[antibody]] production.
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| Mutations in the genes encoding [[CD278|ICOS]], [[TACI]], [[CD19]], [[CD20]], [[CD21]], [[CD80]] and [[BAFF_receptor|BAFFR]] have been identified as causative of CVID.<ref name="CVID new look at old disease" /><ref name="pmid18254984">{{cite journal |vauthors=Salzer U, Neumann C, Thiel J|display-authors=etal |title=Screening of functional and positional candidate genes in families with common variable immunodeficiency |journal=BMC Immunol. |volume=9 |pages=3 |year=2008 |pmid=18254984 |doi=10.1186/1471-2172-9-3 |pmc=2268914 |issue=1}}</ref><ref name="pmid17173844">{{cite journal |vauthors=Blanco-Quirós A, Solís-Sánchez P, Garrote-Adrados JA, Arranz-Sanz E |title=Common variable immunodeficiency. Old questions are getting clearer |journal=Allergol Immunopathol (Madr) |volume=34 |issue=6 |pages=263–75 |year=2006 |pmid=17173844 |doi=10.1157/13095875 |url=http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0102&rev=105&vol=34&num=6&pag=263 |hdl=10261/71519 |access-date=2008-03-01 |archive-url=https://web.archive.org/web/20090521130240/http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0102&rev=105&vol=34&num=6&pag=263 |archive-date=2009-05-21 |url-status=dead }}</ref> Susceptibility to CVID may also be linked to the [[Major histocompatibility complex|Major Histocompatibility Complex]] (MHC) of the genome, particularly to DR-DQ haplotypes.<ref>{{cite journal|last1=O Olerup|first1=O|last2=Smith|first2=CI|last3=Björkander|first3=J|last4=Hammarström|first4=L|title=Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency.|journal=PNAS|date=Nov 15, 1992|volume=89|issue=22|pages=10653–10657|pmc=50399|pmid=1438261|doi=10.1073/pnas.89.22.10653|bibcode=1992PNAS...8910653O}}</ref> A mutation in the [[NFKB2]] gene has recently been shown to cause CVID-like symptoms in a murine model. The frequency of this NFKB2 mutation in the CVID population is, however, yet to be established.<ref>{{cite journal|last=Chen|first=Karin |author2=Emily M. Coonrod |author3=Attila Kumánovics |author4=Zechariah F. Franks |author5=Jacob D. Durtschi |author6=Rebecca L. Margraf |author7=Wilfred Wu |author8=Nahla M. Heikal |author9=Nancy H. Augustine |author10=Perry G. Ridge |author11=Harry R. Hill |author12=Lynn B. Jorde |author13=Andrew S. Weyrich |author14=Guy A. Zimmerman |author15=Adi V. Gundlapalli |author16=John F. Bohnsack |author17=Karl V. Voelkerding |title=Germline Mutations in NFKB2 Implicate the Noncanonical NF-κB Pathway in the Pathogenesis of Common Variable Immunodeficiency.|journal=The American Journal of Human Genetics|date=17 October 2013|doi=10.1016/j.ajhg.2013.09.009|pmid=24140114 |volume=93 |issue=5 |pages=812–24 |pmc=3824125}}</ref>
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| == Diagnosis ==
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| According to a European registry study, the mean age at onset of symptoms was 26.3 years old.<ref name="CVID epi and research">{{cite journal|last1=Bonilla|first1=Francisco A.|last2=Geha|first2=Raif S.|title=Common Variable Immunodeficiency|journal=Pediatric Research|date=2009|volume=65|issue=5|pages=13R–19R|doi=10.1203/pdr.0b013e31819dbf88|pmid=19190529}}</ref> As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if:<ref name="Update in Understanding" />
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| * the person presents with a marked decrease of serum [[IgG]] levels (<4.5 g/L) and a marked decrease below the lower limit of normal for age in at least one of the isotypes [[IgM]] or [[IgA]];
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| * the person is four years of age or older;
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| * the person lacks antibody immune response to protein antigens or immunization.
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| 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.
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| Diagnosis is difficult because of the diversity of phenotypes seen in people with CVID. For example, serum immunoglobulin levels in people with CVID vary greatly. Generally, people can be grouped as follows: no immunoglobulin production, immunoglobulin (Ig) M production only, or both normal IgM and IgG production.<ref name="CVID diagnosis" /> Additionally, B cell numbers are also highly variable. 12% of people have no detectable B cells, 12% have reduced B cells, and 54% are within the normal range.<ref name="Update in Understanding" /> In general, people with CVID display higher frequencies of [[naive B cell]]s and lower frequencies of class-switched [[memory B cells]]. Frequencies of other B cell populations, such as IgD [[memory B cells]], [[transitional B cells]], and [[CD21]] B cells, are also affected, and are associated with specific disease features. Although CVID is often thought of as a serum immunoglobulin and B cell-mediated disease, T cells can display abnormal behavior. Affected individuals typically present with low frequencies of CD4<sup>+</sup>, a T-cell marker, and decreased circulation of [[regulatory T cells]] and [[Natural killer T cell|iNKT cell]]. Notably, approximately 10% of people display CD4<sup>+</sup> T cell counts lower than 200 cells/mm<sup>3</sup>; this particular phenotype of CVID has been named LOCID (Late Onset Combined Immunodeficiency), and has a poorer prognosis than classical CVID.
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| ===Types===
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| {| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
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| |-
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| ! Type
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| ! [[OMIM]]
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| ! Gene
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| | CVID1
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| | {{OMIM2|607594}}
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| | ''[[CD278|ICOS]]''
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| |-
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| | CVID2
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| | {{OMIM2|240500}}
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| | ''[[TACI]]''
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| |-
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| | CVID3
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| | {{OMIM2|613493}}
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| | ''[[CD19]]''
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| |-
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| | CVID4
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| | {{OMIM2|613494}}
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| | ''[[TNFRSF13C]]''
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| |-
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| | CVID5
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| | {{OMIM2|613495}}
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| | ''[[CD20]]''
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| |-
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| | CVID6
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| | {{OMIM2|613496}}
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| | ''[[CD81]]''
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| |}
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| The following types of CVID have been identified, and correspond to mutations in different gene segments.
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| ==Treatment== | | ==Treatment== |
| | The mainstay of treatment for CVID is [[immunoglobulin replacement therapy]], which helps to reduce the frequency and severity of infections. This can be administered intravenously (IVIG) or subcutaneously (SCIG). In addition to immunoglobulin therapy, patients may require antibiotics to treat or prevent infections. Management of associated autoimmune or inflammatory conditions may involve the use of immunosuppressive medications. |
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| Treatment consists of immunoglobulin replacement therapy, which replenishes Ig subtypes that the person lacks. This treatment is given at frequent intervals for life, and is thought to help reduce bacterial infections and boost immune function.<ref>{{cite web|title=Primary immunodeficiency|url=http://www.mayoclinic.org/diseases-conditions/primary-immunodeficiency/basics/treatment/con-20031958|website=Mayo Clinic|accessdate=17 February 2016}}</ref> Before therapy begins, plasma donations are tested for known blood-borne pathogens, then pooled and processed to obtain concentrated [[IgG]] samples. Infusions can be administered in three different forms: intravenously (IVIg):,<ref name="pmid16604243">{{cite journal |vauthors=Pourpak Z, Aghamohammadi A, Sedighipour L|display-authors=etal |title=Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency |journal=J Microbiol Immunol Infect |volume=39 |issue=2 |pages=114–20 |year=2006 |pmid=16604243 |doi= |url=http://www.jmii.org/content/abstracts/v39n2p114.php |format=abstract}}</ref> subcutaneously (SCIg), and intramuscularly (IMIg).
| | ==Prognosis== |
| | The prognosis for individuals with CVID varies depending on the severity of the condition and the presence of complications. With appropriate treatment, many patients can lead relatively normal lives, although they may still experience recurrent infections and other health issues. |
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| The administration of [[intravenous immunoglobulins]] requires the insertion of a cannula or needle in a vein, usually in the arms or hands. Because highly concentrated product is used, IVIg infusions take place every 3 to 4 weeks. Subcutaneous infusions slowly release the Ig serum underneath the skin, again through a needle, and takes place every week.<ref>{{cite web|last1=Schwartz|first1=Robert A|last2=Modak|first2=Rohit|last3=Modak|first3=Prema|title=Common Variable Immunodeficiency Treatment and Management|url=http://emedicine.medscape.com/article/1051103-treatment|website=Medscape|accessdate=17 February 2016}}</ref> Intramuscular infusions are no longer widely used, as they can be painful and are more likely to cause reactions.
| | ==Related pages== |
| | | * [[Primary immunodeficiency]] |
| People often experience adverse side effects to immunoglobulin infusions, including:
| | * [[Immunoglobulin therapy]] |
| * swelling at the insertion site (common in SCIG)
| | * [[Autoimmune disease]] |
| * chills
| | * [[Lymphoma]] |
| * headache
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| * nausea (common in IVIG)
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| * fatigue (common in IVIG)
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| * muscle aches and pain, or joint pain
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| * fever (common in IVIG and rare in SCIG)
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| * [[hives]] (rare) | |
| * thrombotic events (rare)
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| * aseptic meningitis (rare, more common in people with SLE)
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| * [[anaphylactic shock]] (very rare) | |
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| 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.<ref name="Update in Understanding" /> In some cases, antibiotics are used to fight chronic lung disease resulting from CVID.<ref name="immune deficiency foundation">{{cite web|title=Common Variable Immune Deficiency|url=http://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/common-variable-immune-deficiency/|website=Immune Deficiency Foundation|accessdate=16 February 2016}}</ref> The outlook for people varies greatly depending on their level of lung and other organ damage prior to diagnosis and treatment.
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| ==Epidemiology==
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| CVID has an estimated prevalence of about 1:50,000 in caucasians.<ref>{{eMedicine|derm|870|Common Variable Immunodeficiency : Article by Robert A Schwartz}}</ref> The disease seems to be less prevalent amongst Asians and African-Americans. Males and females are equally affected; however, among children, boys predominate.<ref name="CVID diagnosis" /> A recent study of people in European with primary immunodeficiencies found that 30% had CVID, as opposed to a different immunodeficiency.<ref name="CVID new look at old disease" /> 10-25% of people inherited the disease, typically through autosomal-dominant inheritance. Given the rarity of the disease, it is not yet possible to generalize on disease prevalence among ethnic and racial groups. CVID shortens the life-span; but no study currently has a median age recorded. One study suggests the median age of death for men and women is 42 and 44 years old, respectively but most patients involved in the study are still alive. <ref name="many faces of CVID" /> Those people with accompanying disorders had the worst prognosis and those people with CVID only had frequent infections had the longest survival rates, with life expectancy almost equalling that of the general UK population.<ref>{{Cite journal|last=Chapel|first=Helen|last2=Cunningham-Rundles|first2=Charlotte|date=2009-06-01|title=Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions|journal=British Journal of Haematology|language=en|volume=145|issue=6|pages=709–727|doi=10.1111/j.1365-2141.2009.07669.x|issn=1365-2141|pmc=2718064|pmid=19344423}}</ref> Additionally, people with CVID with one or more noninfectious complications have an 11 times higher risk of death as compared to people with only infections.
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| ==History==
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| <ref name="Update in Understanding">{{cite journal|last1=Chapel|first1=Helen|last2=Cunningham-Rundles|first2=Charlotte|title=Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions|journal=British Journal of Haematology|date=2009|volume=145|issue=6|pages=709–727|doi=10.1111/j.1365-2141.2009.07669.x|pmid=19344423|pmc=2718064}}</ref>
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| [[Charles Alderson Janeway|Charles Janeway Sr.]] is generally credited with the first description of a case of CVID in 1953.<ref>{{cite journal |vauthors=Janeway CA, Apt L, Gitlin D | year = 1953 | title = Agammaglobulinemia | url = | journal = Trans Assoc Am Physicians | volume = 66 | issue = | pages = 200–2 | pmid = 13136263 }}</ref> The case involved a 39-year-old who had recurrent infections, bronchiectasis, and meningitis.<ref name="CVID new look at old disease">{{cite journal|last1=Park|first1=Miguel A|last2=Ti|first2=James T|last3=Hagan|first3=John B|last4=Maddox|first4=Daniel E|last5=Abraham|first5=Roshini S|title=Common variable immunodeficiency: a new look at an old disease|journal=The Lancet|date=2008|volume=372|issue=9637|pages=9–15|doi=10.1016/s0140-6736(08)61199-x |pmid=18692715}}</ref> Though described in 1953, there was no standard definition for CVID until the 1990s, which caused widespread confusion during diagnosis. During the 1990s, the European Society for Immunodeficiency (ESID) and Pan-American Group for Immunodeficiency (PAGID) developed diagnostic criteria, including minimum age of diagnosis and the need to exclude other conditions, to describe the disease. These criteria were published in 1999 and since that time, some aspects, like increasing the minimum age, have been changed. | |
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| ==Research==
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| Current research is aimed at studying large cohorts of people with CVID in an attempt to better understand age of onset, as well as mechanism, genetic factors, and progression of the disease.<ref name="CVID diagnosis" />
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| Funding for research in the US is provided by the National Institutes of Health. Key research in the UK was previously funded by the Primary Immunodeficiency Association (PiA) until its closure in January 2012,<ref>{{cite web |url=http://www.ukpin.org.uk/home/PIA-archive/index.htm |title=Archived copy |accessdate=2012-10-26 |url-status=dead |archiveurl=https://web.archive.org/web/20120913082130/http://www.ukpin.org.uk/home/PIA-archive/index.htm |archivedate=2012-09-13 }}</ref> and funding is raised through the annual Jeans for Genes campaign. Current efforts are aimed at studying the following:<ref name="Update in Understanding" />
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| * Causes of complications. Little is known about why such diverse complications arise during treatment | |
| *Underlying genetic factors. Though many polymorphisms and mutations have been identified, their respective roles in CVID development are poorly understood, and not represented in all people with CVID.
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| *Finding new ways to study CVID. Given that CVID arises from more than one gene, [[gene knock-out]] methods are unlikely to be helpful. It is necessary to seek out disease related polymorphisms by screening large populations of people with CVID, but this is challenging given the rarity of the disease.
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| ==References==
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| {{Reflist}}
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| * {{cite journal |author1=Moris G. |author2=Garcia-Monco JC | year = 1999 | title = The Challenge of Drug-Induced Aseptic Meningitis | url = | journal = Archives of Internal Medicine | volume = 159 | issue = 11| pages = 1185–1194 | doi = 10.1001/archinte.159.11.1185 | pmid = 10371226 | doi-access = free }} (IVIG and Aseptic Meningitis, association with SLE)
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| == External links == | | == External links == |
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| *[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cvid GeneReviews/NCBI/NIH/UW entry on Common Variable Immune Deficiency Overview] | | *[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cvid GeneReviews/NCBI/NIH/UW entry on Common Variable Immune Deficiency Overview] |
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| {{Immune disorders}} | | {{Immune disorders}} |
| {{Cell surface receptor deficiencies}} | | {{Cell surface receptor deficiencies}} |
| | | {{stub}} |
| [[Category:Predominantly antibody deficiencies]] | | [[Category:Predominantly antibody deficiencies]] |
| [[Category:Noninfectious immunodeficiency-related cutaneous conditions]] | | [[Category:Noninfectious immunodeficiency-related cutaneous conditions]] |
| {{dictionary-stub1}}
| | [[Category:Immunodeficiency disorders]] |
| | [[Category:Autoimmune diseases]] |
