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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.
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.
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.
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.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Abnormal lymphocyte count
MedGen UID:
663425
Concept ID:
C0580550
Finding
Any abnormality in the total number of lymphocytes in the blood.
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.
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.
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.
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.
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).
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.
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.
Abnormal circulating IgG concentration
MedGen UID:
1687987
Concept ID:
C5139422
Finding
An abnormal deviation from normal levels of IgG immunoglobulin in blood.

Professional guidelines

PubMed

Tipu HN, Ahmed D
J Pak Med Assoc 2020 Dec;70(12(B)):2403-2407. doi: 10.47391/JPMA.512. PMID: 33475552
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

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
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
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
Bonnekoh H, Butze M, Kallinich T, Kambe N, Kokolakis G, Krause K
Acta Derm Venereol 2020 Mar 25;100(7):adv00091. doi: 10.2340/00015555-3427. PMID: 32147748Free PMC Article
Pappo AS
Eur J Cancer 2003 Dec;39(18):2651-61. doi: 10.1016/j.ejca.2003.06.001. PMID: 14642927

Diagnosis

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
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
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
Routes J, Verbsky J
Curr Allergy Asthma Rep 2018 May 10;18(6):34. doi: 10.1007/s11882-018-0783-9. PMID: 29749587
Tschachler E
Clin Dermatol 2014 Mar-Apr;32(2):286-9. doi: 10.1016/j.clindermatol.2013.08.012. PMID: 24559565

Therapy

Janes H, Buchbinder S
Curr Opin HIV AIDS 2023 Nov 1;18(6):349-356. Epub 2023 Sep 11 doi: 10.1097/COH.0000000000000818. PMID: 37712852Free PMC Article
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
Haneke E
Curr Probl Dermatol 1989;18:283-9. doi: 10.1159/000416866. PMID: 2663371
Pichler E, Fritsch P
Curr Probl Dermatol 1989;18:203-9. doi: 10.1159/000416857. PMID: 2472931
Greenwald EF
Clin Obstet Gynecol 1975 Dec;18(4):61-86. doi: 10.1097/00003081-197512000-00007. PMID: 55329

Prognosis

Matsuoka S, Adusei-Poku MA, Abana CZ, Duker EO, Bonney EY, Ofori SB, Parbie PK, Okazaki M, Kawana-Tachikawa A, Ishikawa K, Ampofo WK, Matano T
Jpn J Infect Dis 2022 Jul 22;75(4):395-397. Epub 2021 Dec 28 doi: 10.7883/yoken.JJID.2021.573. PMID: 34980705
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
Hamarsheh O
Int J Infect Dis 2020 Jan;90:18-20. Epub 2019 Oct 21 doi: 10.1016/j.ijid.2019.10.019. PMID: 31648004
Wyatt CM, Murphy B
Semin Dial 2005 Nov-Dec;18(6):495-8. doi: 10.1111/j.1525-139X.2005.00095.x. PMID: 16398712
Greenwald EF
Clin Obstet Gynecol 1975 Dec;18(4):61-86. doi: 10.1097/00003081-197512000-00007. PMID: 55329

Clinical prediction guides

Wang J, Zhou F, Jiang MB, Xu ZH, Ni YH, Wu QS
Hum Vaccin Immunother 2022 Dec 31;18(1):1938922. Epub 2021 Jun 22 doi: 10.1080/21645515.2021.1938922. PMID: 34156902Free PMC Article
Latysheva E, Rodina Y, Sizyakina L, Totolian A, Tuzankina I
Immunotherapy 2020 Apr;12(5):299-309. Epub 2020 Mar 26 doi: 10.2217/imt-2020-0012. PMID: 32212944
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
Cettomai D, Kwasa JK, Birbeck GL, Price RW, Cohen CR, Bukusi EA, Kendi C, Meyer AC
Muscle Nerve 2013 Oct;48(4):516-24. Epub 2013 Aug 27 doi: 10.1002/mus.23795. PMID: 24037693Free PMC Article
Nieves DS, Phipps RP, Pollock SJ, Ochs HD, Zhu Q, Scott GA, Ryan CK, Kobayashi I, Rossi TM, Goldsmith LA
Arch Dermatol 2004 Apr;140(4):466-72. doi: 10.1001/archderm.140.4.466. PMID: 15096376

Recent systematic reviews

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
Patel P, Rose CE, Kjetland EF, Downs JA, Mbabazi PS, Sabin K, Chege W, Watts DH, Secor WE
Int J Infect Dis 2021 Jan;102:544-553. Epub 2020 Nov 3 doi: 10.1016/j.ijid.2020.10.088. PMID: 33157296Free PMC Article
Heidary M, Nasiri MJ, Mirsaeidi M, Jazi FM, Khoshnood S, Drancourt M, Darban-Sarokhalil D
J Cell Physiol 2019 Jul;234(7):9994-10001. Epub 2018 Dec 12 doi: 10.1002/jcp.27859. PMID: 30548598
Vancampfort D, Stubbs B, Mugisha J
Afr Health Sci 2018 Jun;18(2):394-406. doi: 10.4314/ahs.v18i2.25. PMID: 30602967Free PMC Article
Uthman OA, Nduka C, Watson SI, Mills EJ, Kengne AP, Jaffar SS, Clarke A, Moradi T, Ekström AM, Lilford R
BMC Infect Dis 2018 Jun 5;18(1):258. doi: 10.1186/s12879-018-3162-1. PMID: 29866059Free PMC Article

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