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MHC class II deficiency(BLS)

MedGen UID:
444051
Concept ID:
C2931418
Disease or Syndrome
Synonyms: Bare Lymphocyte Syndrome; Bare lymphocyte syndrome 2; BARE LYMPHOCYTE SYNDROME, TYPE II, COMPLEMENTATION GROUP A; BLS 2; BLS, TYPE II; SCID, HLA Class 2-Negative; SCID, HLA CLASS II-NEGATIVE; Severe combined immunodeficiency, HLA class II negative
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).
 
Genes (locations): CIITA (16p13.13); RFX5 (1q21.3); RFXANK (19p13.11); RFXAP (13q13.3)
 
Monarch Initiative: MONDO:0008855
OMIM®: 209920
OMIM® Phenotypic series: PS209920
Orphanet: ORPHA572

Definition

MHC class II deficiency (MHC2D), also known as bare lymphocyte syndrome type II (BLS type II), is a rare autosomal recessive primary immunodeficiency showing genetic heterogeneity. The disorder is characterized by the loss of expression of MHC class II antigens (HLA-DR, HLA-DQ, and HLA-DP) on antigen-presenting cells (APCs) resulting from mutations in regulatory genes required for proper transcription of the MHC class II genes. Affected individuals present in early infancy with severe recurrent infections (bacteria, viruses, fungi, and protozoa), usually affecting the gastrointestinal and respiratory tracts. Protracted diarrhea and failure to thrive is often present. About 20% of patients develop autoimmune features, mainly cytopenias. Laboratory studies show reduced CD4+ T cell counts with an inverted CD4:CD8 ratio, hypogammaglobulinemia, and abnormal lymphocyte proliferation to foreign antigens. Death in infancy or early childhood often occurs, although some patients may have longer survival. MHC type II deficiency may not detected by newborn screening for T-cell receptor excision circles (TRECs). Bone marrow transplantation may be curative, although complications are common (summary by Hanna and Etzioni, 2014; El Hawary et al., 2019). In HLA class II deficiency, the abnormal expression of HLA molecules has been shown to be secondary to defective synthesis (Lisowska-Grospierre et al., 1985), due in turn to an abnormal transacting regulatory gene located outside the major histocompatibility complex (MHC) (Marcadet et al., 1985; de Preval et al., 1985). The transacting regulatory factor, known as RFX, binds to class II promoters and is defective in hereditary HLA deficiency type II, otherwise known as the 'bare lymphocyte syndrome.' The failure of HLA expression leads to immunodeficiency affecting both cellular and humoral responses to antigens. DeSandro et al. (1999) reviewed the molecular bases of the several forms of MHC deficiency. Genetic Heterogeneity of MHC Class II Deficiency MHC2D2 (620815) is caused by mutation in the RFXANK gene (603200); MHC2D3 (620816) and MHC2D5 (620818) are caused by mutation in the RFX5 gene (601863); and MHC2D4 (620817) is caused by mutation in the RFXAP gene (601861). See also MHC class I deficiency (MHC1D1; 604571). [from OMIM]

Professional guidelines

PubMed

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
Picard C, Fischer A
Immunol Allergy Clin North Am 2010 May;30(2):173-8. doi: 10.1016/j.iac.2010.01.001. PMID: 20493394

Recent clinical studies

Etiology

Belaid B, Lamara Mahammed L, Drali O, Oussaid AM, Touri NS, Melzi S, Dehimi A, Berkani LM, Merah F, Larab Z, Allam I, Khemici O, Kirane SY, Boutaba M, Belbouab R, Bekkakcha H, Guedouar A, Chelali A, Baamara B, Noui D, Baaziz H, Rezak R, Azzouz SM, Aichaoui M, Moktefi A, Benhatchi RM, Oussalah M, Benaissa N, Laredj A, Bouchetara A, Adria A, Habireche B, Tounsi N, Dahmoun F, Touati R, Boucenna H, Bouferoua F, Sekfali L, Bouhafs N, Aboura R, Kherra S, Inouri Y, Dib S, Medouri N, Khelfaoui N, Redjedal A, Zelaci A, Yahiaoui S, Medjadj S, Touhami TK, Kadi A, Amireche F, Frada I, Houasnia S, Benarab K, Boubidi C, Ferhani Y, Benalioua H, Sokhal S, Benamar N, Aggoune S, Hadji K, Bellouti A, Rahmoune H, Boutrid N, Okka K, Ammour A, Saadoune H, Amroun M, Belhadj H, Ghanem A, Abbaz H, Boudrioua S, Zebiche B, Ayad A, Hamadache Z, Ouaras N, Achour N, Bouchair N, Boudiaf H, Bekkat-Berkani D, Maouche H, Bouzrar Z, Aissat L, Ibsaine O, Bioud B, Kedji L, Dahlouk D, Bensmina M, Radoui A, Bessahraoui M, Bensaadi N, Mekki A, Zeroual Z, Chan KW, Leung D, Tebaibia A, Ayoub S, Mekideche D, Gharnaout M, Casanova JL, Puel A, Lau YL, Cherif N, Ladj S, Smati L, Boukari R, Benhalla N, Djidjik R
Front Immunol 2022;13:900091. Epub 2022 Apr 21 doi: 10.3389/fimmu.2022.900091. PMID: 35529857Free PMC Article
Çağdaş D, Pehlivantürk Kizılkan M, Tagiyev A, Emiralioğlu N, Keleş A, Yalçın E, Doğru D, Özçelik U, Kiper N, Tezcan İ
Eur Ann Allergy Clin Immunol 2020 Nov;52(6):271-276. Epub 2020 Nov 3 doi: 10.23822/EurAnnACI.1764-1489.151. PMID: 32372587
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
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
Villard J, Mach B, Reith W
Immunobiology 1997 Dec;198(1-3):264-72. doi: 10.1016/S0171-2985(97)80046-0. PMID: 9442397

Diagnosis

Belaid B, Lamara Mahammed L, Drali O, Oussaid AM, Touri NS, Melzi S, Dehimi A, Berkani LM, Merah F, Larab Z, Allam I, Khemici O, Kirane SY, Boutaba M, Belbouab R, Bekkakcha H, Guedouar A, Chelali A, Baamara B, Noui D, Baaziz H, Rezak R, Azzouz SM, Aichaoui M, Moktefi A, Benhatchi RM, Oussalah M, Benaissa N, Laredj A, Bouchetara A, Adria A, Habireche B, Tounsi N, Dahmoun F, Touati R, Boucenna H, Bouferoua F, Sekfali L, Bouhafs N, Aboura R, Kherra S, Inouri Y, Dib S, Medouri N, Khelfaoui N, Redjedal A, Zelaci A, Yahiaoui S, Medjadj S, Touhami TK, Kadi A, Amireche F, Frada I, Houasnia S, Benarab K, Boubidi C, Ferhani Y, Benalioua H, Sokhal S, Benamar N, Aggoune S, Hadji K, Bellouti A, Rahmoune H, Boutrid N, Okka K, Ammour A, Saadoune H, Amroun M, Belhadj H, Ghanem A, Abbaz H, Boudrioua S, Zebiche B, Ayad A, Hamadache Z, Ouaras N, Achour N, Bouchair N, Boudiaf H, Bekkat-Berkani D, Maouche H, Bouzrar Z, Aissat L, Ibsaine O, Bioud B, Kedji L, Dahlouk D, Bensmina M, Radoui A, Bessahraoui M, Bensaadi N, Mekki A, Zeroual Z, Chan KW, Leung D, Tebaibia A, Ayoub S, Mekideche D, Gharnaout M, Casanova JL, Puel A, Lau YL, Cherif N, Ladj S, Smati L, Boukari R, Benhalla N, Djidjik R
Front Immunol 2022;13:900091. Epub 2022 Apr 21 doi: 10.3389/fimmu.2022.900091. PMID: 35529857Free PMC Article
Çağdaş D, Pehlivantürk Kizılkan M, Tagiyev A, Emiralioğlu N, Keleş A, Yalçın E, Doğru D, Özçelik U, Kiper N, Tezcan İ
Eur Ann Allergy Clin Immunol 2020 Nov;52(6):271-276. Epub 2020 Nov 3 doi: 10.23822/EurAnnACI.1764-1489.151. PMID: 32372587
Lum SH, Anderson C, McNaughton P, Engelhardt KR, MacKenzie B, Watson H, Al-Mousa H, Al-Herz W, Al-Saud B, Mohammed R, Al-Zahrani DM, Alghamdi HA, Goronfolah L, Nademi Z, Habibollah S, Flinn AM, Shillitoe B, Owens S, Williams E, Emonts M, Hambleton S, Abinun M, Flood T, Cant A, Gennery AR, Slatter M
Blood 2020 Mar 19;135(12):954-973. doi: 10.1182/blood.2019002690. PMID: 31932845
El Hawary RE, Mauracher AA, Meshaal SS, Eldash A, Abd Elaziz DS, Alkady R, Lotfy S, Opitz L, Galal NM, Boutros JA, Pachlopnik Schmid J, Elmarsafy AM
J Allergy Clin Immunol Pract 2019 Mar;7(3):856-863. Epub 2018 Aug 28 doi: 10.1016/j.jaip.2018.07.046. PMID: 30170160
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

Therapy

Damoiseaux M, Damoiseaux J, Pico-Knijnenburg I, van der Burg M, Bredius R, van Well G
Clin Immunol 2022 Feb;235:108932. Epub 2022 Jan 19 doi: 10.1016/j.clim.2022.108932. PMID: 35065305
Lum SH, Anderson C, McNaughton P, Engelhardt KR, MacKenzie B, Watson H, Al-Mousa H, Al-Herz W, Al-Saud B, Mohammed R, Al-Zahrani DM, Alghamdi HA, Goronfolah L, Nademi Z, Habibollah S, Flinn AM, Shillitoe B, Owens S, Williams E, Emonts M, Hambleton S, Abinun M, Flood T, Cant A, Gennery AR, Slatter M
Blood 2020 Mar 19;135(12):954-973. doi: 10.1182/blood.2019002690. PMID: 31932845
Alyasin S, Abolnezhadian F, Khoshkhui M
Iran J Immunol 2015 Sep;12(3):219-25. PMID: 26412640
Parvaneh N, Shahmahmoudi S, Tabatabai H, Zahraei M, Mousavi T, Esteghamati AR, Gooya MM, Mamishi S, Nategh R, Kew OM
J Clin Virol 2007 Jun;39(2):145-8. Epub 2007 May 16 doi: 10.1016/j.jcv.2007.04.002. PMID: 17509935
Gonc EN, Turul T, Yordam N, Ersoy F
J Pediatr Endocrinol Metab 2003 Dec;16(9):1307-9. doi: 10.1515/jpem.2003.16.9.1307. PMID: 14714756

Prognosis

Çağdaş D, Pehlivantürk Kizılkan M, Tagiyev A, Emiralioğlu N, Keleş A, Yalçın E, Doğru D, Özçelik U, Kiper N, Tezcan İ
Eur Ann Allergy Clin Immunol 2020 Nov;52(6):271-276. Epub 2020 Nov 3 doi: 10.23822/EurAnnACI.1764-1489.151. PMID: 32372587
Lum SH, Anderson C, McNaughton P, Engelhardt KR, MacKenzie B, Watson H, Al-Mousa H, Al-Herz W, Al-Saud B, Mohammed R, Al-Zahrani DM, Alghamdi HA, Goronfolah L, Nademi Z, Habibollah S, Flinn AM, Shillitoe B, Owens S, Williams E, Emonts M, Hambleton S, Abinun M, Flood T, Cant A, Gennery AR, Slatter M
Blood 2020 Mar 19;135(12):954-973. doi: 10.1182/blood.2019002690. PMID: 31932845
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
Picard C, Fischer A
Immunol Allergy Clin North Am 2010 May;30(2):173-8. doi: 10.1016/j.iac.2010.01.001. PMID: 20493394

Clinical prediction guides

Belaid B, Lamara Mahammed L, Drali O, Oussaid AM, Touri NS, Melzi S, Dehimi A, Berkani LM, Merah F, Larab Z, Allam I, Khemici O, Kirane SY, Boutaba M, Belbouab R, Bekkakcha H, Guedouar A, Chelali A, Baamara B, Noui D, Baaziz H, Rezak R, Azzouz SM, Aichaoui M, Moktefi A, Benhatchi RM, Oussalah M, Benaissa N, Laredj A, Bouchetara A, Adria A, Habireche B, Tounsi N, Dahmoun F, Touati R, Boucenna H, Bouferoua F, Sekfali L, Bouhafs N, Aboura R, Kherra S, Inouri Y, Dib S, Medouri N, Khelfaoui N, Redjedal A, Zelaci A, Yahiaoui S, Medjadj S, Touhami TK, Kadi A, Amireche F, Frada I, Houasnia S, Benarab K, Boubidi C, Ferhani Y, Benalioua H, Sokhal S, Benamar N, Aggoune S, Hadji K, Bellouti A, Rahmoune H, Boutrid N, Okka K, Ammour A, Saadoune H, Amroun M, Belhadj H, Ghanem A, Abbaz H, Boudrioua S, Zebiche B, Ayad A, Hamadache Z, Ouaras N, Achour N, Bouchair N, Boudiaf H, Bekkat-Berkani D, Maouche H, Bouzrar Z, Aissat L, Ibsaine O, Bioud B, Kedji L, Dahlouk D, Bensmina M, Radoui A, Bessahraoui M, Bensaadi N, Mekki A, Zeroual Z, Chan KW, Leung D, Tebaibia A, Ayoub S, Mekideche D, Gharnaout M, Casanova JL, Puel A, Lau YL, Cherif N, Ladj S, Smati L, Boukari R, Benhalla N, Djidjik R
Front Immunol 2022;13:900091. Epub 2022 Apr 21 doi: 10.3389/fimmu.2022.900091. PMID: 35529857Free PMC Article
Abolnezhadian F, Dehghani R, Dehnavi S, Khodadadi A, Shohan M
Immunol Res 2020 Aug;68(4):225-231. doi: 10.1007/s12026-020-09141-9. PMID: 32578129
Aluri J, Desai M, Gupta M, Dalvi A, Terance A, Rosenzweig SD, Stoddard JL, Niemela JE, Tamankar V, Mhatre S, Bargir U, Kulkarni M, Shah N, Aggarwal A, Lashkari HP, Krishna V, Govindaraj G, Kalra M, Madkaikar M
Front Immunol 2019;10:23. Epub 2019 Feb 4 doi: 10.3389/fimmu.2019.00023. PMID: 30778343Free PMC Article
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
Naamane H, El Maataoui O, Ailal F, Barakat A, Bennani S, Najib J, Hassar M, Saile R, Bousfiha AA
Eur J Pediatr 2010 Sep;169(9):1069-74. Epub 2010 Apr 23 doi: 10.1007/s00431-010-1179-6. PMID: 20414676

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