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Common variable immunodeficiency(CVID)

MedGen UID:
40407
Concept ID:
C0009447
Disease or Syndrome
Synonyms: Common variable agammaglobulinemia; Common variable hypogamma-globulinemia; CVID
SNOMED CT: Common variable immunodeficiency (191010004); CVID - common variable immunodeficiency (191010004); Idiopathic immunoglobulin deficiency (191010004); Primary antibody deficiency (191010004); Primary hypogammaglobulinemia (191010004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Related genes: IRF2BP2, TNFRSF13C, IL21, ICOS, TNFRSF13B, IKZF1, NFKB2, NFKB1, CR2, LRBA, CD81, MS4A1, CD19
 
Monarch Initiative: MONDO:0015517
OMIM®: 607594
OMIM® Phenotypic series: PS607594
Orphanet: ORPHA1572

Definition

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. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Fevang B
Expert Rev Clin Immunol 2023 Jun;19(6):627-638. Epub 2023 Apr 6 doi: 10.1080/1744666X.2023.2198208. PMID: 36996348
Green PHR, Paski S, Ko CW, Rubio-Tapia A
Gastroenterology 2022 Nov;163(5):1461-1469. Epub 2022 Sep 19 doi: 10.1053/j.gastro.2022.07.086. PMID: 36137844
Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A
J Investig Allergol Clin Immunol 2020;30(1):14-34. Epub 2019 Feb 11 doi: 10.18176/jiaci.0388. PMID: 30741636

Recent clinical studies

Etiology

Remiker A, Bolling K, Verbsky J
Med Clin North Am 2024 Jan;108(1):107-121. Epub 2023 Jul 21 doi: 10.1016/j.mcna.2023.06.012. PMID: 37951645
Leone P, Vacca A, Dammacco F, Racanelli V
Int J Mol Sci 2018 Feb 2;19(2) doi: 10.3390/ijms19020451. PMID: 29393912Free PMC Article
Song J, Lleo A, Yang GX, Zhang W, Bowlus CL, Gershwin ME, Leung PSC
Clin Rev Allergy Immunol 2018 Dec;55(3):340-351. doi: 10.1007/s12016-017-8638-z. PMID: 28785926Free PMC Article
Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarström L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K
J Allergy Clin Immunol Pract 2016 Jan-Feb;4(1):38-59. Epub 2015 Nov 7 doi: 10.1016/j.jaip.2015.07.025. PMID: 26563668Free PMC Article
Tam JS, Routes JM
Am J Rhinol Allergy 2013 Jul-Aug;27(4):260-5. doi: 10.2500/ajra.2013.27.3899. PMID: 23883805Free PMC Article

Diagnosis

Remiker A, Bolling K, Verbsky J
Med Clin North Am 2024 Jan;108(1):107-121. Epub 2023 Jul 21 doi: 10.1016/j.mcna.2023.06.012. PMID: 37951645
Peng XP, Caballero-Oteyza A, Grimbacher B
Annu Rev Pathol 2023 Jan 24;18:283-310. Epub 2022 Oct 20 doi: 10.1146/annurev-pathmechdis-031521-024229. PMID: 36266261
Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A
J Investig Allergol Clin Immunol 2020;30(1):14-34. Epub 2019 Feb 11 doi: 10.18176/jiaci.0388. PMID: 30741636
Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel SY, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaitla PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM
J Allergy Clin Immunol Pract 2017 Jul-Aug;5(4):938-945. Epub 2017 Mar 25 doi: 10.1016/j.jaip.2017.01.021. PMID: 28351785
Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarström L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K
J Allergy Clin Immunol Pract 2016 Jan-Feb;4(1):38-59. Epub 2015 Nov 7 doi: 10.1016/j.jaip.2015.07.025. PMID: 26563668Free PMC Article

Therapy

Fevang B
Expert Rev Clin Immunol 2023 Jun;19(6):627-638. Epub 2023 Apr 6 doi: 10.1080/1744666X.2023.2198208. PMID: 36996348
Lamers OAC, Smits BM, Leavis HL, de Bree GJ, Cunningham-Rundles C, Dalm VASH, Ho HE, Hurst JR, IJspeert H, Prevaes SMPJ, Robinson A, van Stigt AC, Terheggen-Lagro S, van de Ven AAJM, Warnatz K, van de Wijgert JHHM, van Montfrans J
Front Immunol 2021;12:606099. Epub 2021 Apr 15 doi: 10.3389/fimmu.2021.606099. PMID: 33936030Free PMC Article
Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A
J Investig Allergol Clin Immunol 2020;30(1):14-34. Epub 2019 Feb 11 doi: 10.18176/jiaci.0388. PMID: 30741636
Leone P, Vacca A, Dammacco F, Racanelli V
Int J Mol Sci 2018 Feb 2;19(2) doi: 10.3390/ijms19020451. PMID: 29393912Free PMC Article
Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, Mackay F
Cytokine Growth Factor Rev 2013 Jun;24(3):203-15. Epub 2013 May 15 doi: 10.1016/j.cytogfr.2013.04.003. PMID: 23684423Free PMC Article

Prognosis

Gray PE, David C
J Allergy Clin Immunol Pract 2023 Jun;11(6):1602-1622. Epub 2023 Apr 28 doi: 10.1016/j.jaip.2023.04.018. PMID: 37119983
Fevang B
Expert Rev Clin Immunol 2023 Jun;19(6):627-638. Epub 2023 Apr 6 doi: 10.1080/1744666X.2023.2198208. PMID: 36996348
Lamers OAC, Smits BM, Leavis HL, de Bree GJ, Cunningham-Rundles C, Dalm VASH, Ho HE, Hurst JR, IJspeert H, Prevaes SMPJ, Robinson A, van Stigt AC, Terheggen-Lagro S, van de Ven AAJM, Warnatz K, van de Wijgert JHHM, van Montfrans J
Front Immunol 2021;12:606099. Epub 2021 Apr 15 doi: 10.3389/fimmu.2021.606099. PMID: 33936030Free PMC Article
Song J, Lleo A, Yang GX, Zhang W, Bowlus CL, Gershwin ME, Leung PSC
Clin Rev Allergy Immunol 2018 Dec;55(3):340-351. doi: 10.1007/s12016-017-8638-z. PMID: 28785926Free PMC Article
Baldovino S, Menegatti E, Roccatello D, Sciascia S
Adv Exp Med Biol 2017;1031:497-509. doi: 10.1007/978-3-319-67144-4_26. PMID: 29214588

Clinical prediction guides

Fevang B
Expert Rev Clin Immunol 2023 Jun;19(6):627-638. Epub 2023 Apr 6 doi: 10.1080/1744666X.2023.2198208. PMID: 36996348
Ho HE, Cunningham-Rundles C
Front Immunol 2022;13:857050. Epub 2022 Mar 11 doi: 10.3389/fimmu.2022.857050. PMID: 35359997Free PMC Article
Pittman ME
Am J Surg Pathol 2022 Jan 1;46(1):e55-e63. doi: 10.1097/PAS.0000000000001667. PMID: 33481383
Singh BK, Singh S
Reumatismo 2020 Nov 19;72(3):154-169. doi: 10.4081/reumatismo.2020.1303. PMID: 33213128
Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel SY, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaitla PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM
J Allergy Clin Immunol Pract 2017 Jul-Aug;5(4):938-945. Epub 2017 Mar 25 doi: 10.1016/j.jaip.2017.01.021. PMID: 28351785

Recent systematic reviews

Bintalib HM, van de Ven A, Jacob J, Davidsen JR, Fevang B, Hanitsch LG, Malphettes M, van Montfrans J, Maglione PJ, Milito C, Routes J, Warnatz K, Hurst JR
Front Immunol 2023;14:1190235. Epub 2023 May 8 doi: 10.3389/fimmu.2023.1190235. PMID: 37223103Free PMC Article
Lamers OAC, Smits BM, Leavis HL, de Bree GJ, Cunningham-Rundles C, Dalm VASH, Ho HE, Hurst JR, IJspeert H, Prevaes SMPJ, Robinson A, van Stigt AC, Terheggen-Lagro S, van de Ven AAJM, Warnatz K, van de Wijgert JHHM, van Montfrans J
Front Immunol 2021;12:606099. Epub 2021 Apr 15 doi: 10.3389/fimmu.2021.606099. PMID: 33936030Free PMC Article
Rizvi FS, Zainaldain H, Rafiemanesh H, Jamee M, Hossein-Khannazer N, Hamedifar H, Sabzevari A, Yazdani R, Abolhassani H, Aghamohammadi A, Azizi G
Expert Rev Clin Immunol 2020 Dec;16(12):1227-1235. Epub 2020 Dec 7 doi: 10.1080/1744666X.2021.1850272. PMID: 33203275
Ramzi N, Jamee M, Bakhtiyari M, Rafiemanesh H, Zainaldain H, Tavakol M, Rezaei A, Kalvandi M, Zian Z, Mohammadi H, Jadidi-Niaragh F, Yazdani R, Abolhassani H, Aghamohammadi A, Azizi G
Pediatr Pulmonol 2020 Feb;55(2):292-299. Epub 2019 Dec 13 doi: 10.1002/ppul.24599. PMID: 31833673
Mazza JM, Lin SY
Int Forum Allergy Rhinol 2016 Oct;6(10):1029-1033. Epub 2016 May 17 doi: 10.1002/alr.21789. PMID: 27187624

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