| H00093 | |
| H number | H00093 |
| Name | Combined immunodeficiency |
| 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 |
| Network | nt06509(H00093) DNA replication nt06528(H00093) Calcium signaling nt06530(H00093) PI3K signaling |
| 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] [KO:K26401] (IMD97) PIK3CG [HSA:5294] [KO:K21289] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| 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 619802 |
| 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 PMID:9737224 AUTHORS Ten RM. TITLE Primary immunodeficiencies. JOURNAL Mayo Clin Proc 73:865-72 (1998) DOI:10.4065/73.9.865 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 PMID:33054089 (PIK3CG) 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 |