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MHC class II deficiency 3

MedGen UID:
347175
Concept ID:
C1859536
Disease or Syndrome
Synonym: Bare lymphocyte syndrome, type II, complementation group c
 
Monarch Initiative: MONDO:0971014
OMIM®: 620816

Definition

MHC class II deficiency-3 (MHC2D3) is a rare autosomal recessive immunodeficiency characterized by the onset of recurrent and persistent infections from birth. Infectious agents include bacteria, viruses, fungi, and protozoa, usually affecting the respiratory and gastrointestinal tract. Laboratory studies show decreased CD4+ T cells, hypogammaglobulinemia, an inverted CD4:CD8 ratio, and absence of MHC type II antigens (HLA-DR, -DQ, and -DP) on the surface of antigen-presenting cells. Most patients die in infancy or early childhood unless they undergo bone marrow transplantation, which can be curative, although complications are common. Rare patients may survive longer, even without bone marrow transplant. MHC class II deficiency may not be detected by newborn T-cell receptor excision circle (TREC) screening (summary by El Hawary et al., 2019; Mousavi Khorshidi et al., 2023). For a discussion of genetic heterogeneity of MHC class II deficiency, see MHC2D1 (209920). [from OMIM]

Additional description

From MedlinePlus Genetics
BLS II is typically diagnosed in the first year of life. Most affected infants have persistent infections in the respiratory, gastrointestinal, and urinary tracts. Because of the infections, affected infants have difficulty absorbing nutrients (malabsorption), and they grow more slowly than their peers. Eventually, the persistent infections lead to organ failure. Without treatment, individuals with BLS II usually do not survive past early childhood.

In people with BLS II, infection-fighting white blood cells (lymphocytes) are missing specialized proteins on their surface called major histocompatibility complex (MHC) class II proteins, which is where the condition got its name. Because BLS II is the most common and best studied form of a group of related conditions, it is often referred to as simply bare lymphocyte syndrome (BLS).

Bare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined immunodeficiency (CID). People with BLS II lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system.  https://medlineplus.gov/genetics/condition/bare-lymphocyte-syndrome-type-ii

Professional guidelines

PubMed

Ben Salem I, Khemiri H, Drechsel O, Arbi M, Böttcher S, Mekki N, Ben Fraj I, Souiai O, Yahyaoui M, Ben Farhat E, Meddeb Z, Touzi H, Ben Mustapha I, BenKahla A, Ouederni M, Barbouche MR, Diedrich S, Triki H, Haddad-Boubaker S
J Med Virol 2024 Sep;96(9):e29918. doi: 10.1002/jmv.29918. PMID: 39311394
Korkmaz SB, Karaselek MA, Aytekin SE, Tokgoz H, Reisli I, Guner S, Keles S
Int J Immunogenet 2023 Aug;50(4):177-184. Epub 2023 Jun 12 doi: 10.1111/iji.12624. PMID: 37308802
Mishra A, Gupta M, Dalvi A, Ghosh K, Madkaikar M
J Clin Immunol 2014 Apr;34(3):316-22. Epub 2014 Feb 18 doi: 10.1007/s10875-014-9993-7. PMID: 24535004

Recent clinical studies

Etiology

Gulec Koksal Z, Bilgic Eltan S, Topyildiz E, Sezer A, Keles S, Celebi Celik F, Ozhan Kont A, Gemici Karaaslan B, Sefer AP, Karali Z, Arik E, Ozek Yucel E, Akcal O, Karakurt LT, Yorgun Altunbas M, Yalcin K, Uygun V, Ozek G, Babayeva R, Aydogmus C, Ozcan D, Cavkaytar O, Keskin O, Kilic SS, Kiykim A, Arikoglu T, Genel F, Gulez N, Guner SN, Karaca NE, Reisli I, Kutukculer N, Altintas DU, Ozen A, Karakoc Aydiner E, Baris S
J Allergy Clin Immunol Pract 2024 Sep;12(9):2490-2502.e6. Epub 2024 Jul 10 doi: 10.1016/j.jaip.2024.06.046. PMID: 38996837
Kopp MA, Meisel C, Liebscher T, Watzlawick R, Cinelli P, Schweizerhof O, Blex C, Lübstorf T, Prilipp E, Niedeggen A, Druschel C, Schaser KD, Wanner GA, Curt A, Lindemann G, Nugeva N, Fehlings MG, Vajkoczy P, Cabraja M, Dengler J, Ertel W, Ekkernkamp A, Rehahn K, Martus P, Volk HD, Unterwalder N, Kölsch U, Brommer B, Hellmann RC, Baumgartner E, Hirt J, Geurtz LC, Saidy RRO, Prüss H, Laginha I, Failli V, Grittner U, Dirnagl U, Schwab JM
Brain 2023 Aug 1;146(8):3500-3512. doi: 10.1093/brain/awad092. PMID: 37370200Free PMC Article
Hanna S, Etzioni A
J Allergy Clin Immunol 2014 Aug;134(2):269-75. Epub 2014 Jul 4 doi: 10.1016/j.jaci.2014.06.001. PMID: 25001848
Fischer A
Immunodefic Rev 1992;3(2):83-100. PMID: 1554500
Gyódi E, Benczur M, Pálffy G, Tálas M, Petrányi G, Földes I, Hollán SR
Hum Immunol 1982 Jun;4(3):209-17. doi: 10.1016/0198-8859(82)90036-2. PMID: 6181031

Diagnosis

Gulec Koksal Z, Bilgic Eltan S, Topyildiz E, Sezer A, Keles S, Celebi Celik F, Ozhan Kont A, Gemici Karaaslan B, Sefer AP, Karali Z, Arik E, Ozek Yucel E, Akcal O, Karakurt LT, Yorgun Altunbas M, Yalcin K, Uygun V, Ozek G, Babayeva R, Aydogmus C, Ozcan D, Cavkaytar O, Keskin O, Kilic SS, Kiykim A, Arikoglu T, Genel F, Gulez N, Guner SN, Karaca NE, Reisli I, Kutukculer N, Altintas DU, Ozen A, Karakoc Aydiner E, Baris S
J Allergy Clin Immunol Pract 2024 Sep;12(9):2490-2502.e6. Epub 2024 Jul 10 doi: 10.1016/j.jaip.2024.06.046. PMID: 38996837
Ka Y, Katano I, Nishinaka E, Welcker J, Mochizuki M, Kawai K, Goto M, Tomiyama K, Ogura T, Yamamoto T, Ito M, Ito R, Takahashi R
Immunol Lett 2021 Jan;229:55-61. Epub 2020 Nov 27 doi: 10.1016/j.imlet.2020.11.011. PMID: 33253759
Brogan P, Eleftheriou D
Pediatr Nephrol 2018 Feb;33(2):187-198. Epub 2017 Aug 7 doi: 10.1007/s00467-017-3597-4. PMID: 28785984Free PMC Article
Hanna S, Etzioni A
J Allergy Clin Immunol 2014 Aug;134(2):269-75. Epub 2014 Jul 4 doi: 10.1016/j.jaci.2014.06.001. PMID: 25001848
Fischer A
Immunodefic Rev 1992;3(2):83-100. PMID: 1554500

Therapy

Eguren-Santamaria I, Fernández de Piérola E, Camps G, Martín-Muñoz P, Campos M, Cuculescu D, Aguilera-Buenosvinos I, Rodríguez López I, Salido-Vallejo R, Alexandru R, De Andrea CE, Álvarez-Gigli L, Berraondo P, Melero I, Sanmamed MF
J Immunother Cancer 2024 Sep 6;12(9) doi: 10.1136/jitc-2023-008516. PMID: 39244214Free PMC Article
Bhakat B, Pal J, Das S, Charaborty SK, SircarMedical NR, Kolkata, RGKar, NorthBengal, Siliguri
J Assoc Physicians India 2023 Jan;71(1):1. PMID: 37116030
Ka Y, Katano I, Nishinaka E, Welcker J, Mochizuki M, Kawai K, Goto M, Tomiyama K, Ogura T, Yamamoto T, Ito M, Ito R, Takahashi R
Immunol Lett 2021 Jan;229:55-61. Epub 2020 Nov 27 doi: 10.1016/j.imlet.2020.11.011. PMID: 33253759
Fischer A
Immunodefic Rev 1992;3(2):83-100. PMID: 1554500
Rynes RI
Clin Rheum Dis 1982 Apr;8(1):29-47. PMID: 6288318

Prognosis

Gulec Koksal Z, Bilgic Eltan S, Topyildiz E, Sezer A, Keles S, Celebi Celik F, Ozhan Kont A, Gemici Karaaslan B, Sefer AP, Karali Z, Arik E, Ozek Yucel E, Akcal O, Karakurt LT, Yorgun Altunbas M, Yalcin K, Uygun V, Ozek G, Babayeva R, Aydogmus C, Ozcan D, Cavkaytar O, Keskin O, Kilic SS, Kiykim A, Arikoglu T, Genel F, Gulez N, Guner SN, Karaca NE, Reisli I, Kutukculer N, Altintas DU, Ozen A, Karakoc Aydiner E, Baris S
J Allergy Clin Immunol Pract 2024 Sep;12(9):2490-2502.e6. Epub 2024 Jul 10 doi: 10.1016/j.jaip.2024.06.046. PMID: 38996837
Brogan P, Eleftheriou D
Pediatr Nephrol 2018 Feb;33(2):187-198. Epub 2017 Aug 7 doi: 10.1007/s00467-017-3597-4. PMID: 28785984Free PMC Article
Farrokhi S, Shabani M, Aryan Z, Zoghi S, Krolo A, Boztug K, Rezaei N
Allergol Immunopathol (Madr) 2018 May-Jun;46(3):263-275. Epub 2017 Jul 1 doi: 10.1016/j.aller.2017.04.006. PMID: 28676232
Siepermann M, Gudowius S, Beltz K, Strier U, Feyen O, Troeger A, Göbel U, Laws HJ, Kögler G, Meisel R, Dilloo D, Niehues T
Pediatr Transplant 2011 Jun;15(4):E80-6. Epub 2010 Mar 4 doi: 10.1111/j.1399-3046.2010.01292.x. PMID: 20214747
Ruiz-Cabello F, Klein E, Garrido F
Immunol Lett 1991 Aug;29(3):181-9. doi: 10.1016/0165-2478(91)90168-a. PMID: 1769705

Clinical prediction guides

Gulec Koksal Z, Bilgic Eltan S, Topyildiz E, Sezer A, Keles S, Celebi Celik F, Ozhan Kont A, Gemici Karaaslan B, Sefer AP, Karali Z, Arik E, Ozek Yucel E, Akcal O, Karakurt LT, Yorgun Altunbas M, Yalcin K, Uygun V, Ozek G, Babayeva R, Aydogmus C, Ozcan D, Cavkaytar O, Keskin O, Kilic SS, Kiykim A, Arikoglu T, Genel F, Gulez N, Guner SN, Karaca NE, Reisli I, Kutukculer N, Altintas DU, Ozen A, Karakoc Aydiner E, Baris S
J Allergy Clin Immunol Pract 2024 Sep;12(9):2490-2502.e6. Epub 2024 Jul 10 doi: 10.1016/j.jaip.2024.06.046. PMID: 38996837
Brehm MA, Kenney LL, Wiles MV, Low BE, Tisch RM, Burzenski L, Mueller C, Greiner DL, Shultz LD
FASEB J 2019 Mar;33(3):3137-3151. Epub 2018 Nov 1 doi: 10.1096/fj.201800636R. PMID: 30383447Free PMC Article
Aono S, Tatsumi T, Yoshioka T, Tawara S, Nishio A, Onishi Y, Fukutomi K, Nakabori T, Kodama T, Shigekawa M, Hikita H, Sakamori R, Takahashi T, Suemizu H, Takehara T
Biochem Biophys Res Commun 2018 Sep 10;503(3):1457-1464. Epub 2018 Jul 20 doi: 10.1016/j.bbrc.2018.07.063. PMID: 30033102
Brogan P, Eleftheriou D
Pediatr Nephrol 2018 Feb;33(2):187-198. Epub 2017 Aug 7 doi: 10.1007/s00467-017-3597-4. PMID: 28785984Free PMC Article
Gyódi E, Benczur M, Pálffy G, Tálas M, Petrányi G, Földes I, Hollán SR
Hum Immunol 1982 Jun;4(3):209-17. doi: 10.1016/0198-8859(82)90036-2. PMID: 6181031

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