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Immunodeficiency 18(IMD18)

MedGen UID:
816457
•Concept ID:
C3810127
•
Disease or Syndrome
Synonyms: CD3-EPSILON DEFICIENCY; CD3epsilon deficiency; IMD18
 
Gene (location): CD3E (11q23.3)
 
Monarch Initiative: MONDO:0014278
OMIM®: 615615

Definition

Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004). [from OMIM]

Clinical features

From HPO
Recurrent gastroenteritis
MedGen UID:
815158
•Concept ID:
C3808828
•
Finding
Increased susceptibility to gastroenteritis, an infectious inflammationof the stomach and small intestines manifested by signs and symptoms such as diarheas and abdominal pain, as manifested by recurrent episodes of gastroenteritis.
See: Feature record | Search on this feature
Recurrent pneumonia
MedGen UID:
195802
•Concept ID:
C0694550
•
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
See: Feature record | Search on this feature
Recurrent respiratory infections
MedGen UID:
812812
•Concept ID:
C3806482
•
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
See: Feature record | Search on this feature
Immunodeficiency
MedGen UID:
7034
•Concept ID:
C0021051
•
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
See: Feature record | Search on this feature
Lymphopenia
MedGen UID:
7418
•Concept ID:
C0024312
•
Disease or Syndrome
A reduced number of lymphocytes in the blood.
See: Feature record | Search on this feature
Decreased circulating total IgM
MedGen UID:
116095
•Concept ID:
C0239989
•
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
See: Feature record | Search on this feature
Abnormal lymphocyte count
MedGen UID:
663425
•Concept ID:
C0580550
•
Finding
Any abnormality in the total number of lymphocytes in the blood.
See: Feature record | Search on this feature
Recurrent otitis media
MedGen UID:
155436
•Concept ID:
C0747085
•
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
See: Feature record | Search on this feature
Reduced natural killer cell count
MedGen UID:
383765
•Concept ID:
C1855767
•
Finding
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system with an ability to mediate cytotoxicity and produce cytokines after the ligation of a germline-encoded activation receptor.
See: Feature record | Search on this feature
Abnormal B cell count
MedGen UID:
866853
•Concept ID:
C4021208
•
Finding
A deviation from the normal count of B cells, i.e., the cells that are formed in the bone marrow, migrate to the peripheral lymphatic system, and mature into plasma cells or memory cells.
See: Feature record | Search on this feature
Defective T cell proliferation
MedGen UID:
868165
•Concept ID:
C4022557
•
Cell or Molecular Dysfunction
A reduced ability of a T cell population to expand by cell division following T cell activation.
See: Feature record | Search on this feature
Decreased circulating total IgA
MedGen UID:
871140
•Concept ID:
C4025611
•
Finding
Undetectable serum immunoglobulin A level at a value < 5 mg/dL (0.05 g/L).
See: Feature record | Search on this feature
Decreased proportion of CD3-positive T cells
MedGen UID:
1369785
•Concept ID:
C4477053
•
Finding
Any abnormality in the proportion of CD3-positive T cells relative to the total number of T cells.
See: Feature record | Search on this feature
Decreased proportion of CD4-positive T cells
MedGen UID:
1698933
•Concept ID:
C5139203
•
Finding
A reduction in the proportion of CD4-positive T cells relative to the total number of T cells.
See: Feature record | Search on this feature
Abnormal circulating IgG concentration
MedGen UID:
1687987
•Concept ID:
C5139422
•
Finding
An abnormal deviation from normal levels of IgG immunoglobulin in blood.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Clinical and Laboratory Characteristics of Primary Immunodeficiency Patients from a Tertiary Care Center in Pakistan.
Tipu HN, Ahmed D
J Pak Med Assoc 2020 Dec;70(12(B)):2403-2407. doi: 10.47391/JPMA.512. PMID: 33475552
Primary immunodeficiency diseases in Latin America: first report from eight countries participating in the LAGID. Latin American Group for Primary Immunodeficiency Diseases.
Zelazko M, Carneiro-Sampaio M, Cornejo de Luigi M, Garcia de Olarte D, Porras Madrigal O, Berrón Perez R, Cabello A, Rostan MV, Sorensen RU
J Clin Immunol 1998 Mar;18(2):161-6. doi: 10.1023/a:1023255102170. PMID: 9533660

Recent clinical studies

Etiology

Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years.
Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, Mateja A, Laidlaw E, Manion M, Roby G, Higgins J, Kuriakose S, Walkiewicz MA, Similuk M, Leiding JW, Freeman AF, Sheikh V, Sereti I
N Engl J Med 2023 May 4;388(18):1680-1691. doi: 10.1056/NEJMoa2202348. PMID: 37133586Free PMC Article
HIV and liver disease.
Navarro J
AIDS Rev 2022;25(2):87-96. doi: 10.24875/AIDSRev.M22000052. PMID: 35901073
Therapeutic options for CTLA-4 insufficiency.
Egg D, Rump IC, Mitsuiki N, Rojas-Restrepo J, Maccari ME, Schwab C, Gabrysch A, Warnatz K, Goldacker S, Patiño V, Wolff D, Okada S, Hayakawa S, Shikama Y, Kanda K, Imai K, Sotomatsu M, Kuwashima M, Kamiya T, Morio T, Matsumoto K, Mori T, Yoshimoto Y, Dybedal I, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Lorenz HM, Sullivan KE, Heimall J, Moutschen M, Litzman J, Recher M, Albert MH, Hauck F, Seneviratne S, Pachlopnik Schmid J, Kolios A, Unglik G, Klemann C, Snapper S, Giulino-Roth L, Svaton M, Platt CD, Hambleton S, Neth O, Gosse G, Reinsch S, Holzinger D, Kim YJ, Bakhtiar S, Atschekzei F, Schmidt R, Sogkas G, Chandrakasan S, Rae W, Derfalvi B, Marquart HV, Ozen A, Kiykim A, Karakoc-Aydiner E, Králíčková P, de Bree G, Kiritsi D, Seidel MG, Kobbe R, Dantzer J, Alsina L, Armangue T, Lougaris V, Agyeman P, Nyström S, Buchbinder D, Arkwright PD, Grimbacher B
J Allergy Clin Immunol 2022 Feb;149(2):736-746. Epub 2021 Jun 7 doi: 10.1016/j.jaci.2021.04.039. PMID: 34111452
Efficacy and economics of targeted panel versus whole-exome sequencing in 878 patients with suspected primary immunodeficiency.
Platt CD, Zaman F, Bainter W, Stafstrom K, Almutairi A, Reigle M, Weeks S, Geha RS, Chou J; International Consortium for Immunodeficiencies
J Allergy Clin Immunol 2021 Feb;147(2):723-726. Epub 2020 Sep 2 doi: 10.1016/j.jaci.2020.08.022. PMID: 32888943Free PMC Article
Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study.
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article

Diagnosis

Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years.
Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, Mateja A, Laidlaw E, Manion M, Roby G, Higgins J, Kuriakose S, Walkiewicz MA, Similuk M, Leiding JW, Freeman AF, Sheikh V, Sereti I
N Engl J Med 2023 May 4;388(18):1680-1691. doi: 10.1056/NEJMoa2202348. PMID: 37133586Free PMC Article
Common Variable Immunodeficiency: More Pathways than Roads to Rome.
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
Therapeutic options for CTLA-4 insufficiency.
Egg D, Rump IC, Mitsuiki N, Rojas-Restrepo J, Maccari ME, Schwab C, Gabrysch A, Warnatz K, Goldacker S, Patiño V, Wolff D, Okada S, Hayakawa S, Shikama Y, Kanda K, Imai K, Sotomatsu M, Kuwashima M, Kamiya T, Morio T, Matsumoto K, Mori T, Yoshimoto Y, Dybedal I, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Lorenz HM, Sullivan KE, Heimall J, Moutschen M, Litzman J, Recher M, Albert MH, Hauck F, Seneviratne S, Pachlopnik Schmid J, Kolios A, Unglik G, Klemann C, Snapper S, Giulino-Roth L, Svaton M, Platt CD, Hambleton S, Neth O, Gosse G, Reinsch S, Holzinger D, Kim YJ, Bakhtiar S, Atschekzei F, Schmidt R, Sogkas G, Chandrakasan S, Rae W, Derfalvi B, Marquart HV, Ozen A, Kiykim A, Karakoc-Aydiner E, Králíčková P, de Bree G, Kiritsi D, Seidel MG, Kobbe R, Dantzer J, Alsina L, Armangue T, Lougaris V, Agyeman P, Nyström S, Buchbinder D, Arkwright PD, Grimbacher B
J Allergy Clin Immunol 2022 Feb;149(2):736-746. Epub 2021 Jun 7 doi: 10.1016/j.jaci.2021.04.039. PMID: 34111452
Efficacy and economics of targeted panel versus whole-exome sequencing in 878 patients with suspected primary immunodeficiency.
Platt CD, Zaman F, Bainter W, Stafstrom K, Almutairi A, Reigle M, Weeks S, Geha RS, Chou J; International Consortium for Immunodeficiencies
J Allergy Clin Immunol 2021 Feb;147(2):723-726. Epub 2020 Sep 2 doi: 10.1016/j.jaci.2020.08.022. PMID: 32888943Free PMC Article
WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.
Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM
J Clin Immunol 2019 Aug;39(6):532-556. Epub 2019 Jul 16 doi: 10.1007/s10875-019-00665-w. PMID: 31313072Free PMC Article

Therapy

Breast implant illness: scientific evidence of its existence.
Cohen Tervaert JW, Mohazab N, Redmond D, van Eeden C, Osman M
Expert Rev Clin Immunol 2022 Jan;18(1):15-29. Epub 2022 Jan 5 doi: 10.1080/1744666X.2022.2010546. PMID: 34882509
Nurse led home-based care for people with HIV/AIDS.
Wood EM, Zani B, Esterhuizen TM, Young T
BMC Health Serv Res 2018 Mar 27;18(1):219. doi: 10.1186/s12913-018-3002-4. PMID: 29587719Free PMC Article
Second- and Third-line Antiretroviral Therapy for Children and Adolescents: A Scoping Review.
Lazarus E, Nicol S, Frigati L, Penazzato M, Cotton MF, Centeno-Tablante E, Violari A, Nicol L
Pediatr Infect Dis J 2017 May;36(5):492-499. doi: 10.1097/INF.0000000000001481. PMID: 28403052
Pre-Exposure Prophylaxis for HIV: Evidence and Perspectives.
Nikolopoulos GK, Christaki E, Paraskevis D, Bonovas S
Curr Pharm Des 2017;23(18):2579-2591. doi: 10.2174/1381612823666170329145053. PMID: 28356043
Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study.
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article

Prognosis

Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years.
Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, Mateja A, Laidlaw E, Manion M, Roby G, Higgins J, Kuriakose S, Walkiewicz MA, Similuk M, Leiding JW, Freeman AF, Sheikh V, Sereti I
N Engl J Med 2023 May 4;388(18):1680-1691. doi: 10.1056/NEJMoa2202348. PMID: 37133586Free PMC Article
Waldenström macroglobulinemia and relationship to immune deficiency.
Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595
Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function.
Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA
Blood 2021 May 6;137(18):2450-2462. doi: 10.1182/blood.2020009620. PMID: 33512449Free PMC Article
Very early onset IBD: novel genetic aetiologies.
Batura V, Muise AM
Curr Opin Allergy Clin Immunol 2018 Dec;18(6):470-480. doi: 10.1097/ACI.0000000000000486. PMID: 30299396
Treatment of hairy-cell leukemia.
Lill MC, Golde DW
Blood Rev 1990 Dec;4(4):238-44. doi: 10.1016/0268-960x(90)90003-b. PMID: 1706207

Clinical prediction guides

Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years.
Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, Mateja A, Laidlaw E, Manion M, Roby G, Higgins J, Kuriakose S, Walkiewicz MA, Similuk M, Leiding JW, Freeman AF, Sheikh V, Sereti I
N Engl J Med 2023 May 4;388(18):1680-1691. doi: 10.1056/NEJMoa2202348. PMID: 37133586Free PMC Article
Autoimmune disorders associated with common variable immunodeficiency: prediction, diagnosis, and treatment.
Yazdanpanah N, Rezaei N
Expert Rev Clin Immunol 2022 Dec;18(12):1265-1283. Epub 2022 Oct 17 doi: 10.1080/1744666X.2022.2132938. PMID: 36197300
Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study.
Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D
Arthritis Rheumatol 2017 May;69(5):1016-1027. Epub 2017 Apr 7 doi: 10.1002/art.40049. PMID: 28118533Free PMC Article
Advances in the diagnosis and treatment of chronic granulomatous disease.
Seger RA
Curr Opin Hematol 2011 Jan;18(1):36-41. doi: 10.1097/MOH.0b013e32834115e7. PMID: 21076296
Treatment of hairy-cell leukemia.
Lill MC, Golde DW
Blood Rev 1990 Dec;4(4):238-44. doi: 10.1016/0268-960x(90)90003-b. PMID: 1706207

Recent systematic reviews

HIV-associated infective native aortic aneurysms.
Jönsson A, Ljungquist O, Sörelius K
APMIS 2023 Jan;131(1):3-12. Epub 2022 Oct 1 doi: 10.1111/apm.13273. PMID: 36106509
Tuberculosis Treatment Outcome and Predictors in Africa: A Systematic Review and Meta-Analysis.
Teferi MY, El-Khatib Z, Boltena MT, Andualem AT, Asamoah BO, Biru M, Adane HT
Int J Environ Res Public Health 2021 Oct 12;18(20) doi: 10.3390/ijerph182010678. PMID: 34682420Free PMC Article
The prevalence of depression among adolescent with HIV/AIDS: a systematic review and meta-analysis.
Ayano G, Demelash S, Abraha M, Tsegay L
AIDS Res Ther 2021 Apr 27;18(1):23. doi: 10.1186/s12981-021-00351-1. PMID: 33906698Free PMC Article
Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis.
Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M; IeDEA Southern and Central Africa
Lancet Infect Dis 2010 Apr;10(4):251-61. doi: 10.1016/S1473-3099(10)70026-8. PMID: 20334848Free PMC Article
HIV: mother-to-child transmission.
Volmink J, Marais B
BMJ Clin Evid 2008 Feb 5;2008 PMID: 19450331Free PMC Article

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