KEGG DISEASE: Combined immunodeficiency

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 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
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06509  DNA replication
   H00093  Combined immunodeficiency
Signal transduction
  nt06530  PI3K signaling
   H00093  Combined immunodeficiency
  nt06518  JAK-STAT signaling
   H00093  Combined immunodeficiency
  nt06516  TNF signaling
   H00093  Combined immunodeficiency
  nt06528  Calcium signaling
   H00093  Combined immunodeficiency
Immune system
  nt06537  TCR/BCR signaling
   H00093  Combined immunodeficiency

Pathway

hsa04020 Calcium signaling pathway

hsa04151 PI3K-Akt signaling pathway

hsa04660 T cell receptor signaling pathway

Network

nt06509 DNA replication
nt06516 TNF signaling
nt06518 JAK-STAT signaling
nt06528 Calcium signaling
nt06530 PI3K signaling
nt06537 TCR/BCR signaling

Gene

CD40LG (TNFSF5) [HSA:959] [KO:K03161]
CD40 [HSA:958] [KO:K03160]
PNP [HSA:4860] [KO:K03783]
(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]
(IMD50) MSN [HSA:4478] [KO:K05763]
(IMD55) GINS1 [HSA:9837] [KO:K10732]
(IMD59) HYOU1 [HSA:10525] [KO:K09486]
(IMD71) ARPC1B [HSA:10095] [KO:K05757]
(IMD85) TOM1 [HSA:10043] [KO:K26401]
(IMD97) PIK3CG [HSA:5294] [KO:K21289]
(IMD110) STK4 [HSA:6789] [KO:K04411]
(IMD112) MAP3K14 [HSA:9020] [KO:K04466]
(IMD116) CD8A [HSA:925] [KO:K06458]
(IMD119) ICOSLG [HSA:23308] [KO:K06710]
(IMD120) POLD1 [HSA:5424] [KO:K02327]
(IMD128) COPG1 [HSA:22820] [KO:K17267]

Other DBs

ICD-11:

4A01.1

ICD-10:

D81

MeSH:

D053632

Reference

PMID:17162365

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

PMID:15096561

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

PMID:18424339

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

PMID:17952897

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 (IMD6)

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 (IMD9 IMD10)

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 (IMD11)

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 (IMD12)

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 (IMD15)

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 (IMD16)

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:17277165 (IMD17)

Authors

Recio MJ, Moreno-Pelayo MA, Kilic SS, Guardo AC, Sanal O, Allende LM, Perez-Flores V, Mencia A, Modamio-Hoybjor S, Seoane E, Regueiro JR

Title

Differential biological role of CD3 chains revealed by human immunodeficiencies.

Journal

J Immunol 178:2556-64 (2007)
DOI:10.4049/jimmunol.178.4.2556

Reference

PMID:22985903 (IMD22)

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 (IMD24)

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 (IMD37)

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 (IMD40)

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:8202712 (IMD48)

Authors

Elder ME, Lin D, Clever J, Chan AC, Hope TJ, Weiss A, Parslow TG

Title

Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase.

Journal

Science 264:1596-9 (1994)
DOI:10.1126/science.8202712

Reference

PMID:27405666 (IMD50)

Authors

Lagresle-Peyrou C, Luce S, Ouchani F, Soheili TS, Sadek H, Chouteau M, Durand A, Pic I, Majewski J, Brouzes C, Lambert N, Bohineust A, Verhoeyen E, Cosset FL, Magerus-Chatinet A, Rieux-Laucat F, Gandemer V, Monnier D, Heijmans C, van Gijn M, Dalm VA, Mahlaoui N, Stephan JL, Picard C, Durandy A, Kracker S, Hivroz C, Jabado N, de Saint Basile G, Fischer A, Cavazzana M, Andre-Schmutz I

Title

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

Journal

J Allergy Clin Immunol 138:1681-1689.e8 (2016)
DOI:10.1016/j.jaci.2016.04.032

Reference

PMID:28414293 (IMD55)

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 (IMD59)

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:30254128 (IMD71)

Authors

Brigida I, Zoccolillo M, Cicalese MP, Pfajfer L, Barzaghi F, Scala S, Oleaga-Quintas C, Alvarez-Alvarez JA, Sereni L, Giannelli S, Sartirana C, Dionisio F, Pavesi L, Benavides-Nieto M, Basso-Ricci L, Capasso P, Mazzi B, Rosain J, Marcus N, Lee YN, Somech R, Degano M, Raiola G, Caorsi R, Picco P, Moncada Velez M, Khourieh J, Arias AA, Bousfiha A, Issekutz T, Issekutz A, Boisson B, Dobbs K, Villa A, Lombardo A, Neven B, Moshous D, Casanova JL, Franco JL, Notarangelo LD, Scielzo C, Volpi S, Dupre L, Bustamante J, Gattorno M, Aiuti A

Title

T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency.

Journal

Blood 132:2362-2374 (2018)
DOI:10.1182/blood-2018-07-863431

Reference

PMID:31263572 (IMD85)

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

Reference

PMID:33054089 (IMD97)

Authors

Thian M, Hoeger B, Kamnev A, Poyer F, Kostel Bal S, Caldera M, Jimenez-Heredia R, Huemer J, Pickl WF, Gross M, Ehl S, Lucas CL, Menche J, Hutter C, Attarbaschi A, Dupre L, Boztug K

Title

Germline biallelic PIK3CG mutations in a multifaceted immunodeficiency with immune dysregulation.

Journal

Haematologica 105:e488 (2020)
DOI:10.3324/haematol.2019.231399

Reference

PMID:22174160 (IMD110)

Authors

Nehme NT, Schmid JP, Debeurme F, Andre-Schmutz I, Lim A, Nitschke P, Rieux-Laucat F, Lutz P, Picard C, Mahlaoui N, Fischer A, de Saint Basile G

Title

MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival.

Journal

Blood 119:3458-68 (2012)
DOI:10.1182/blood-2011-09-378364

Reference

PMID:29230214 (IMD112)

Authors

Schlechter N, Glanzmann B, Hoal EG, Schoeman M, Petersen BS, Franke A, Lau YL, Urban M, van Helden PD, Esser MM, Moller M, Kinnear C

Title

Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency.

Journal

Front Immunol 8:1624 (2017)
DOI:10.3389/fimmu.2017.01624

Reference

PMID:11435463 (IMD116)

Authors

de la Calle-Martin O, Hernandez M, Ordi J, Casamitjana N, Arostegui JI, Caragol I, Ferrando M, Labrador M, Rodriguez-Sanchez JL, Espanol T

Title

Familial CD8 deficiency due to a mutation in the CD8 alpha gene.

Journal

J Clin Invest 108:117-23 (2001)
DOI:10.1172/JCI10993

Reference

PMID:30498080 (IMD119)

Authors

Roussel L, Landekic M, Golizeh M, Gavino C, Zhong MC, Chen J, Faubert D, Blanchet-Cohen A, Dansereau L, Parent MA, Marin S, Luo J, Le C, Ford BR, Langelier M, King IL, Divangahi M, Foulkes WD, Veillette A, Vinh DC

Title

Loss of human ICOSL results in combined immunodeficiency.

Journal

J Exp Med 215:3151-3164 (2018)
DOI:10.1084/jem.20180668

Reference

PMID:31449058 (IMD120)

Authors

Conde CD, Petronczki OY, Baris S, Willmann KL, Girardi E, Salzer E, Weitzer S, Ardy RC, Krolo A, Ijspeert H, Kiykim A, Karakoc-Aydiner E, Forster-Waldl E, Kager L, Pickl WF, Superti-Furga G, Martinez J, Loizou JI, Ozen A, van der Burg M, Boztug K

Title

Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress.

Journal

J Clin Invest 129:4194-4206 (2019)
DOI:10.1172/JCI128903

Reference

PMID:33529166 (IMD128)

Authors

Bainter W, Platt CD, Park SY, Stafstrom K, Wallace JG, Peters ZT, Massaad MJ, Becuwe M, Salinas SA, Jones J, Beaussant-Cohen S, Jaber F, Yang JS, Walther TC, Orange JS, Rao C, Rakoff-Nahoum S, Tsokos M, Naseem SUR, Al-Tamemi S, Chou J, Hsu VW, Geha RS

Title

Combined immunodeficiency due to a mutation in the gamma1 subunit of the coat protein I complex.

Journal

J Clin Invest 131:140494 (2021)
DOI:10.1172/JCI140494

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   KEGG VARIANT (11)   
Disease (29)   
   OMIM (29)   
Gene (56)   
   KEGG ORTHOLOGY (28)   
   KEGG GENES (28)   
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