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Immunoglobulin heavy chain deficiency

MedGen UID:
98309
•Concept ID:
C0398692
•
Disease or Syndrome
Synonyms: immunoglobulin heavy chain deficiency; Immunoglobulin heavy chain deletion; Immunoglobulin Heavy Chain Deletion
SNOMED CT: Immunoglobulin heavy chain deficiency (234539005); Immunoglobulin heavy chain deletion (234539005)
 
Monarch Initiative: MONDO:0015697
Orphanet: ORPHA169110

Definition

A disorder that affects the production of complete immunoglobulins. Deletions in the heavy chain genes on chromosome 14 disrupt the synthesis and secretion of properly functioning antibodies resulting in monoclonal populations of truncated heavy chains without covalently bonded light chains. Such deletions have been implicated as playing a significant role in several diseases including leukemias, lymphomas and myelomas. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImmunoglobulin heavy chain deficiency
Follow this link to review classifications for Immunoglobulin heavy chain deficiency in Orphanet.

Professional guidelines

PubMed

EuroFlow-Based Flowcytometric Diagnostic Screening and Classification of Primary Immunodeficiencies of the Lymphoid System.
van Dongen JJM, van der Burg M, Kalina T, Perez-Andres M, Mejstrikova E, Vlkova M, Lopez-Granados E, Wentink M, Kienzler AK, Philippé J, Sousa AE, van Zelm MC, Blanco E, Orfao A
Front Immunol 2019;10:1271. Epub 2019 Jun 13 doi: 10.3389/fimmu.2019.01271. PMID: 31263462Free PMC Article
A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.
Lee YN, Frugoni F, Dobbs K, Walter JE, Giliani S, Gennery AR, Al-Herz W, Haddad E, LeDeist F, Bleesing JH, Henderson LA, Pai SY, Nelson RP, El-Ghoneimy DH, El-Feky RA, Reda SM, Hossny E, Soler-Palacin P, Fuleihan RL, Patel NC, Massaad MJ, Geha RS, Puck JM, Palma P, Cancrini C, Chen K, Vihinen M, Alt FW, Notarangelo LD
J Allergy Clin Immunol 2014 Apr;133(4):1099-108. Epub 2013 Nov 28 doi: 10.1016/j.jaci.2013.10.007. PMID: 24290284Free PMC Article
Clinical criteria for the diagnosis of vascular dementia.
Loeb C
Eur Neurol 1988;28(2):87-92. doi: 10.1159/000116237. PMID: 3131146

Recent clinical studies

Etiology

Diversity of Immunoglobulin (Ig) Isotypes and the Role of Activation-Induced Cytidine Deaminase (AID) in Fish.
Patel B, Banerjee R, Samanta M, Das S
Mol Biotechnol 2018 Jun;60(6):435-453. doi: 10.1007/s12033-018-0081-8. PMID: 29704159
Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy.
Huang ZQ, Raska M, Stewart TJ, Reily C, King RG, Crossman DK, Crowley MR, Hargett A, Zhang Z, Suzuki H, Hall S, Wyatt RJ, Julian BA, Renfrow MB, Gharavi AG, Novak J
J Am Soc Nephrol 2016 Nov;27(11):3278-3284. Epub 2016 Mar 10 doi: 10.1681/ASN.2014101044. PMID: 26966014Free PMC Article
Mutation mismatch repair gene deletions in diffuse large B-cell lymphoma.
Couronné L, Ruminy P, Waultier-Rascalou A, Rainville V, Cornic M, Picquenot JM, Figeac M, Bastard C, Tilly H, Jardin F
Leuk Lymphoma 2013 May;54(5):1079-86. Epub 2012 Nov 15 doi: 10.3109/10428194.2012.739687. PMID: 23066952
TLR-mediated B cell defects and IFN-α in common variable immunodeficiency.
Yu JE, Zhang L, Radigan L, Sanchez-Ramon S, Cunningham-Rundles C
J Clin Immunol 2012 Feb;32(1):50-60. Epub 2011 Nov 3 doi: 10.1007/s10875-011-9602-y. PMID: 22048980Free PMC Article
Monoclonal gammopathies in children.
Gerritsen E, Vossen J, van Tol M, Jol-van der Zijde C, Van der Weijden-Ragas R, Radl J
J Clin Immunol 1989 Jul;9(4):296-305. doi: 10.1007/BF00918661. PMID: 2504763

Diagnosis

Immunoglobulin A nephropathy: a pathophysiology view.
Fabiano RC, Pinheiro SV, Simões E Silva AC
Inflamm Res 2016 Oct;65(10):757-70. Epub 2016 Jun 28 doi: 10.1007/s00011-016-0962-x. PMID: 27351940
Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination.
Li G, Alt FW, Cheng HL, Brush JW, Goff PH, Murphy MM, Franco S, Zhang Y, Zha S
Mol Cell 2008 Sep 5;31(5):631-40. doi: 10.1016/j.molcel.2008.07.017. PMID: 18775323Free PMC Article
IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy.
Novak J, Julian BA, Tomana M, Mestecky J
Semin Nephrol 2008 Jan;28(1):78-87. doi: 10.1016/j.semnephrol.2007.10.009. PMID: 18222349Free PMC Article
Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic leukaemia.
Chen J, McMillan NA
Cancer Biol Ther 2008 Feb;7(2):174-9. Epub 2007 Nov 3 doi: 10.4161/cbt.7.2.5262. PMID: 18059180
BCR mutants deficient in ligand-independent and more sensitive for ligand-dependent signaling.
Pracht C, Gimborn K, Reth M, Huber M
Eur J Immunol 2002 Jun;32(6):1614-20. doi: 10.1002/1521-4141(200206)32:6<1614::AID-IMMU1614>3.0.CO;2-A. PMID: 12115644

Therapy

Pozelimab: First Approval.
Hoy SM
Drugs 2023 Nov;83(16):1551-1557. doi: 10.1007/s40265-023-01955-9. PMID: 37856038
IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy.
Novak J, Julian BA, Tomana M, Mestecky J
Semin Nephrol 2008 Jan;28(1):78-87. doi: 10.1016/j.semnephrol.2007.10.009. PMID: 18222349Free PMC Article
Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic leukaemia.
Chen J, McMillan NA
Cancer Biol Ther 2008 Feb;7(2):174-9. Epub 2007 Nov 3 doi: 10.4161/cbt.7.2.5262. PMID: 18059180
The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease.
Akilesh S, Petkova S, Sproule TJ, Shaffer DJ, Christianson GJ, Roopenian D
J Clin Invest 2004 May;113(9):1328-33. doi: 10.1172/JCI18838. PMID: 15124024Free PMC Article
Human immunoglobulin genes in health and disease.
Alexander A, Rosen S, Buxbaum J
Clin Immunol Rev 1985;4(1):31-94. PMID: 3928220

Prognosis

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency.
Pal Singh S, de Bruijn MJW, de Almeida MP, Meijers RWJ, Nitschke L, Langerak AW, Pillai SY, Stadhouders R, Hendriks RW
Front Immunol 2018;9:1996. Epub 2018 Sep 13 doi: 10.3389/fimmu.2018.01996. PMID: 30271400Free PMC Article
Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic leukaemia.
Chen J, McMillan NA
Cancer Biol Ther 2008 Feb;7(2):174-9. Epub 2007 Nov 3 doi: 10.4161/cbt.7.2.5262. PMID: 18059180
Deficiency of somatic hypermutation of immunoglobulin G transcripts is a better predictor of severe respiratory tract infections than lack of memory B cells in common variable immunodeficiency.
Schejbel L, Marquart H, Andersen V, Permin H, Andersen P, Svejgaard A, Barington T
J Clin Immunol 2005 Jul;25(4):392-403. doi: 10.1007/s10875-005-5034-x. PMID: 16133996
Molecular genetic biomarkers in hematological malignancies.
Bagg A, Cossman J
J Cell Biochem Suppl 1996;25:165-71. PMID: 9027614
Monoclonal gammopathies in children.
Gerritsen E, Vossen J, van Tol M, Jol-van der Zijde C, Van der Weijden-Ragas R, Radl J
J Clin Immunol 1989 Jul;9(4):296-305. doi: 10.1007/BF00918661. PMID: 2504763

Clinical prediction guides

IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development.
Riva F, Ponzoni M, Supino D, Bertilaccio MTS, Polentarutti N, Massara M, Pasqualini F, Carriero R, Innocenzi A, Anselmo A, Veliz-Rodriguez T, Simonetti G, Anders HJ, Caligaris-Cappio F, Mantovani A, Muzio M, Garlanda C
Cancer Immunol Res 2019 Jun;7(6):874-885. Epub 2019 Apr 24 doi: 10.1158/2326-6066.CIR-18-0698. PMID: 31018956Free PMC Article
VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation.
Sethi MK, Thol F, Stadler M, Heuser M, Ganser A, Koenecke C, Pabst O
PLoS One 2017;12(1):e0168096. Epub 2017 Jan 17 doi: 10.1371/journal.pone.0168096. PMID: 28095438Free PMC Article
Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis.
Du L, Peng R, Björkman A, Filipe de Miranda N, Rosner C, Kotnis A, Berglund M, Liu C, Rosenquist R, Enblad G, Sundström C, Hojjat-Farsangi M, Rabbani H, Teixeira MR, Revy P, Durandy A, Zeng Y, Gennery AR, de Villartay JP, Pan-Hammarström Q
J Exp Med 2012 Feb 13;209(2):291-305. Epub 2012 Feb 6 doi: 10.1084/jem.20110325. PMID: 22312109Free PMC Article
Immunoglobulin G subclass deficiency: fact or fancy?
Buckley RH
Curr Allergy Asthma Rep 2002 Sep;2(5):356-60. doi: 10.1007/s11882-002-0067-1. PMID: 12165200
Fragments of immunoglobulins in human faeces.
Haneberg B, Endresen C
Acta Pathol Microbiol Scand C 1976 Feb;84(1):31-6. doi: 10.1111/j.1699-0463.1976.tb03596.x. PMID: 1266624

Recent systematic reviews

Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis.
Kreuzberger N, Damen JA, Trivella M, Estcourt LJ, Aldin A, Umlauff L, Vazquez-Montes MD, Wolff R, Moons KG, Monsef I, Foroutan F, Kreuzer KA, Skoetz N
Cochrane Database Syst Rev 2020 Jul 31;7(7):CD012022. doi: 10.1002/14651858.CD012022.pub2. PMID: 32735048Free PMC Article

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