KEGG   DISEASE: Combined immunodeficiency
Entry
H00093                      Disease                                
Name
Combined immunodeficiency
  Subgroup
Bare lymphocyte syndrome type 1 [DS:H00984]
Bare lymphocyte syndrome type 2 [DS:H00985]
  Supergrp
Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]
Description
The term combined immunodeficiency (CID) is used to distinguish patients with low, but not absent, T-cell function from those with severe CID (SCID) characterized by profound deficiencies of T- and B-cell (and sometimes NK- cell) function. Hyper-IgM syndrome (HIM) represents a group of distinct entities characterized by defective normal or elevated IgM in the presence of diminished IgG and IgA levels. The genetic anomaly in X-linked hyper-IgM syndrome has been mapped to Xq26, and resides in mutations of the CD40 ligand gene. ZAP-70 deficiency is inherited in an autosomal recessive manner. Recurrent and opportunistic infections occur within the first year of life. The mutations in genes responsible for CRAC channel function, ORAI1 and STIM1, cause the defect in Ca2+ influx.
Category
Primary immunodeficiency
Brite
Human diseases [BR:br08402]
 Immune system diseases
  Primary immunodeficiency
   H00093  Combined immunodeficiency
Human diseases in ICD-11 classification [BR:br08403]
 04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H00093  Combined immunodeficiency
Related
pathway
hsa04660  T cell receptor signaling pathway
hsa04662  B cell receptor signaling pathway
hsa04064  NF-kappa B signaling pathway
Network
nt06509  DNA replication
Gene
CD40LG (TNFSF5) [HSA:959] [KO:K03161]
CD40 [HSA:958] [KO:K03160]
PNP [HSA:4860] [KO:K03783]
CD8A [HSA:925] [KO:K06458]
(IMD6) IL2RG [HSA:3561] [KO:K05070]
(IMD9) ORAI1 [HSA:84876] [KO:K16056]
(IMD10) STIM1 [HSA:6786] [KO:K16059]
(IMD11) CARD11 [HSA:84433] [KO:K07367]
(IMD12) MALT1 [HSA:10892] [KO:K07369]
(IMD15) IKBKB [HSA:3551] [KO:K07209]
(IMD16) TNFRSF4 [HSA:7293] [KO:K05142]
(IMD17) CD3G [HSA:917] [KO:K06452]
(IMD22) LCK [HSA:3932] [KO:K05856]
(IMD24) CTPS1 [HSA:1503] [KO:K01937]
(IMD37) BCL10 [HSA:8915] [KO:K07368]
(IMD40) DOCK2 [HSA:1794] [KO:K12367]
(IMD48) ZAP70 [HSA:7535] [KO:K07360]
(IMD55) GINS1 [HSA:9837] [KO:K10732]
(IMD59) HYOU1 [HSA:10525] [KO:K09486]
(IMD85) TOM1 [HSA:10043]
Other DBs
ICD-11: 4A01.1
ICD-10: D81
MeSH: D053632
OMIM: 308230 606843 613179 608957 312863 612782 612783 615206 617638 615468 618204 615592 615593 615607 615758 615897 616098 616433 617827 233600 619510
Reference
  Authors
Kumar A, Teuber SS, Gershwin ME.
  Title
Current perspectives on primary immunodeficiency diseases.
  Journal
Clin Dev Immunol 13:223-59 (2006)
DOI:10.1080/17402520600800705
Reference
PMID:9737224
  Authors
Ten RM.
  Title
Primary immunodeficiencies.
  Journal
Mayo Clin Proc 73:865-72 (1998)
DOI:10.4065/73.9.865
Reference
  Authors
Lim MS, Elenitoba-Johnson KS.
  Title
The molecular pathology of primary immunodeficiencies.
  Journal
J Mol Diagn 6:59-83 (2004)
DOI:10.1016/S1525-1578(10)60493-X
Reference
  Authors
Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.
  Title
Genetic diagnosis of primary immune deficiencies.
  Journal
Immunol Allergy Clin North Am 28:387-412, x (2008)
DOI:10.1016/j.iac.2008.01.004
Reference
  Authors
Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.
  Title
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
  Journal
J Allergy Clin Immunol 120:776-94 (2007)
DOI:10.1016/j.jaci.2007.08.053
Reference
PMID:20004777 (CD40LG, CD40, CD3G, CD8A, ZAP70)
  Authors
Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Hammartrom L, Nonoyama S, Ochs HD, Puck J, Roifman C, Seger R, Wedgwood J
  Title
Primary immunodeficiencies: 2009 update.
  Journal
J Allergy Clin Immunol 124:1161-78 (2009)
DOI:10.1016/j.jaci.2009.10.013
Reference
PMID:30885031 (PNP)
  Authors
Fekrvand S, Yazdani R, Abolhassani H, Ghaffari J, Aghamohammadi A
  Title
The First Purine Nucleoside Phosphorylase Deficiency Patient Resembling IgA Deficiency and a Review of the Literature.
  Journal
Immunol Invest 48:410-430 (2019)
DOI:10.1080/08820139.2019.1570249
Reference
PMID:7883965 (IL2RG)
  Authors
Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS
  Title
Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.
  Journal
J Clin Invest 95:1169-73 (1995)
DOI:10.1172/JCI117765
Reference
PMID:20189884 (ORAI1, STIM1)
  Authors
Feske S, Picard C, Fischer A
  Title
Immunodeficiency due to mutations in ORAI1 and STIM1.
  Journal
Clin Immunol 135:169-82 (2010)
DOI:10.1016/j.clim.2010.01.011
Reference
PMID:23374270 (CARD11)
  Authors
Stepensky P, Keller B, Buchta M, Kienzler AK, Elpeleg O, Somech R, Cohen S, Shachar I, Miosge LA, Schlesier M, Fuchs I, Enders A, Eibel H, Grimbacher B, Warnatz K
  Title
Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.
  Journal
J Allergy Clin Immunol 131:477-85.e1 (2013)
DOI:10.1016/j.jaci.2012.11.050
Reference
PMID:23727036 (MALT1)
  Authors
Jabara HH, Ohsumi T, Chou J, Massaad MJ, Benson H, Megarbane A, Chouery E, Mikhael R, Gorka O, Gewies A, Portales P, Nakayama T, Hosokawa H, Revy P, Herrod H, Le Deist F, Lefranc G, Ruland J, Geha RS
  Title
A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.
  Journal
J Allergy Clin Immunol 132:151-8 (2013)
DOI:10.1016/j.jaci.2013.04.047
Reference
PMID:30337470 (IKBKB)
  Authors
Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida K, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field MA, Burgio G, Morio T, Vinuesa CG, Kanegane H, Cook MC
  Title
Gain-of-function IKBKB mutation causes human combined immune deficiency.
  Journal
J Exp Med 215:2715-2724 (2018)
DOI:10.1084/jem.20180639
Reference
PMID:26215166 (TNFRSF4)
  Authors
Webb GJ, Hirschfield GM, Lane PJ
  Title
OX40, OX40L and Autoimmunity: a Comprehensive Review.
  Journal
Clin Rev Allergy Immunol 50:312-32 (2016)
DOI:10.1007/s12016-015-8498-3
Reference
PMID:22985903 (LCK)
  Authors
Hauck F, Randriamampita C, Martin E, Gerart S, Lambert N, Lim A, Soulier J, Maciorowski Z, Touzot F, Moshous D, Quartier P, Heritier S, Blanche S, Rieux-Laucat F, Brousse N, Callebaut I, Veillette A, Hivroz C, Fischer A, Latour S, Picard C
  Title
Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency.
  Journal
J Allergy Clin Immunol 130:1144-1152.e11 (2012)
DOI:10.1016/j.jaci.2012.07.029
Reference
PMID:24870241 (CTPS1)
  Authors
Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschke P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S
  Title
CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation.
  Journal
Nature 510:288-92 (2014)
DOI:10.1038/nature13386
Reference
PMID:25365219 (BCL10)
  Authors
Torres JM, Martinez-Barricarte R, Garcia-Gomez S, Mazariegos MS, Itan Y, Boisson B, Rholvarez R, Jimenez-Reinoso A, del Pino L, Rodriguez-Pena R, Ferreira A, Hernandez-Jimenez E, Toledano V, Cubillos-Zapata C, Diaz-Almiron M, Lopez-Collazo E, Unzueta-Roch JL, Sanchez-Ramon S, Regueiro JR, Lopez-Granados E, Casanova JL, Perez de Diego R
  Title
Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.
  Journal
J Clin Invest 124:5239-48 (2014)
DOI:10.1172/JCI77493
Reference
PMID:26083206 (DOCK2)
  Authors
Dobbs K, Dominguez Conde C, Zhang SY, Parolini S, Audry M, Chou J, Haapaniemi E, Keles S, Bilic I, Okada S, Massaad MJ, Rounioja S, Alwahadneh AM, Serwas NK, Capuder K, Ciftci E, Felgentreff K, Ohsumi TK, Pedergnana V, Boisson B, Haskologlu S, Ensari A, Schuster M, Moretta A, Itan Y, Patrizi O, Rozenberg F, Lebon P, Saarela J, Knip M, Petrovski S, Goldstein DB, Parrott RE, Savas B, Schambach A, Tabellini G, Bock C, Chatila TA, Comeau AM, Geha RS, Abel L, Buckley RH, Ikinciogullari A, Al-Herz W, Helminen M, Dogu F, Casanova JL, Boztug K, Notarangelo LD
  Title
Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.
  Journal
N Engl J Med 372:2409-22 (2015)
DOI:10.1056/NEJMoa1413462
Reference
PMID:28414293 (GINS1)
  Authors
Cottineau J, Kottemann MC, Lach FP, Kang YH, Vely F, Deenick EK, Lazarov T, Gineau L, Wang Y, Farina A, Chansel M, Lorenzo L, Piperoglou C, Ma CS, Nitschke P, Belkadi A, Itan Y, Boisson B, Jabot-Hanin F, Picard C, Bustamante J, Eidenschenk C, Boucherit S, Aladjidi N, Lacombe D, Barat P, Qasim W, Hurst JA, Pollard AJ, Uhlig HH, Fieschi C, Michon J, Bermudez VP, Abel L, de Villartay JP, Geissmann F, Tangye SG, Hurwitz J, Vivier E, Casanova JL, Smogorzewska A, Jouanguy E
  Title
Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.
  Journal
J Clin Invest 127:1991-2006 (2017)
DOI:10.1172/JCI90727
Reference
PMID:27913302 (HYOU1)
  Authors
Haapaniemi EM, Fogarty CL, Keskitalo S, Katayama S, Vihinen H, Ilander M, Mustjoki S, Krjutskov K, Lehto M, Hautala T, Eriksson O, Jokitalo E, Velagapudi V, Varjosalo M, Seppanen M, Kere J
  Title
Combined immunodeficiency and hypoglycemia associated with mutations in hypoxia upregulated 1.
  Journal
J Allergy Clin Immunol 139:1391-1393.e11 (2017)
DOI:10.1016/j.jaci.2016.09.050
Reference
PMID:31263572 (TOM1)
  Authors
Keskitalo S, Haapaniemi EM, Glumoff V, Liu X, Lehtinen V, Fogarty C, Rajala H, Chiang SC, Mustjoki S, Kovanen P, Lohi J, Bryceson YT, Seppanen M, Kere J, Heiskanen K, Varjosalo M
  Title
Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease.
  Journal
NPJ Genom Med 4:14 (2019)
DOI:10.1038/s41525-019-0088-5
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