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Inborn errors of immunity

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625:, i.e., they are mosaicism in which individuals developing from these post-fertilized ova have cells that do and do not have the altered gene that is responsible for a immune disorder. Depending on the amount and type of cells that express the dysfunctional gene, individuals may not develop the disorder or develop it in varying degrees of severity and/or develop it at a later age than individuals that have the dysfunctional gene in all cells. Usually, individuals with this mosaicism do not pass the defective gene to their offspring. 945:
Shirkani A, Bagheri Z, Salami F, Shad TM, Marzbali MY, Mojtahedi H, Razavi A, Tavakolinia N, Cheraghi T, Tavakol M, Shafiei A, Behniafard N, Ebrahimi SS, Sepahi N, Ghaneimoghadam A, Rezaei A, Kalantari A, Abolhassani H, Rezaei N (February 2024). "Clinical heterogeneity in families with multiple cases of inborn errors of immunity".
334:. This mutation usually causes a complicated medical condition involving several human organ systems. When any one of the disorders in the PID, PIRDs, or IEM classifications is caused by a single gene mutation that disrupts the immune system, it is termed an IEI. Consequently, many IEIs are also termed a PID, PIRDs, and/or IEM. 345:(i.e., IUIS). This relationship was made official in 2008. The number of genes that when mutated to cause specific IEI disorders has steadily rose from less than 10 in the 1980s to the IUIS expert committee's 2022 classification of 485 mutated genes causing these disorders. These numbers are expected to increase further as 1571:
Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, Rundles CC, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Puel A, Puck J, Seppänen MR, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I (October 2022). "The 2022 Update of IUIS Phenotypical Classification for Human Inborn
473:
Combined immunodeficiencies with associated or syndromic features consisting of 69 defective genes causing 68 diseases. These diseases are a set of signs and symptoms characteristic of a particular immune disorder and tend to occur together in people with the same disorder. These disorders include
436:, i.e., an IEI mutation arising after fertilization of an egg, has been shown to lead to offsspring with two different cell populations, one with and one without the IEI gene. Individuals with this mosaicism may develop a mild IEI disorder, an IEI disorder much later in life, or no IEI disorder. 1166:
Nishimura A, Uppuluri R, Raj R, Swaminathan VV, Cheng Y, Abu-Arja RF, Fu B, Laberko A, Albert MH, Hauck F, Bucciol G, Bigley V, Elcombe S, Kharya G, Pronk CJ, Wehr C, Neven B, Warnatz K, Meyts I, Morio T, Gennery AR, Kanegane H (November 2023). "An International Survey of Allogeneic Hematopoietic
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Delavari S, Rasouli SE, Fekrvand S, Chavoshzade Z, Mahdaviani SA, Shirmast P, Sharafian S, Sherkat R, Momen T, Aleyasin S, Ahanchian H, Sadeghi-Shabestari M, Esmaeilzadeh H, Barzamini S, Tarighatmonfared F, Salehi H, Esmaeili M, Marzani Z, Fathi N, Abolnezhadian F, Rad MK, Saeedi-Boroujeni A,
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Patterson AR, Needle GA, Sugiura A, Jennings EQ, Chi C, Steiner KK, Fisher EL, Robertson GL, Bodnya C, Markle JG, Sheldon RD, Jones RG, Gama V, Rathmell JC (August 2024). "Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities".
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Tangye, Stuart G.; Al-Herz, Waleed; Bousfiha, Aziz; Chatila, Talal; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Holland, Steven M.; Klein, Christoph; Morio, Tomohiro; Ochs, Hans D.; Oksenhendler, Eric; Picard, Capucine; Puck, Jennifer; Torgerson, Troy R. (2020).
341:(WHO) established the Inborn Errors of Immunity Committee for the purpose of classifying and identifying immune defects in humans. The committee focused on rare immune diseases. In the 1990s, the WHO decided to focus on more common diseases, and the committee was taken on by the 369:), is under expressed, is overexpressed, or directs the formation of a product with reduced, increased, or no activity. Furthermore, the defective IEI gene in parents may not be expressed in their offspring depending on the IEI gene's 248:. In the early 1950s, he examined an 8-year-old boy who had 19 episodes of pneumonia over a period of 4 years. Expecting that individuals with such a history of repeated infections would have high levels of infection-fighting 759:
Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppänen MR, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I (October 2022).
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and virus. That same year, Dr. Bruton and colleagues published on two other infection-prone patients who also lacked detectable levels of these serum antibodies This particular from of hypogammaglobulinemia, now termed
357:). Thus, the prevalence of IEIs in 2023 was estimated to be between 1 in 1,000 and 1 in 5,000 individuals but this may be an underestimate: its true prevalence may turn out to be as high as 1 in 500 individuals. 511: 809:
Moratti M, Conti F, Giannella M, Ferrari S, Borghesi A (November 2022). "How to: Diagnose inborn errors of intrinsic and innate immunity to viral, bacterial, mycobacterial, and fungal infections".
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Defects in intrinsic and innate immunity consisting of 74 gene defects causing 63 diseases. These diseases include a predisposition to develop bacterial, fungal, parasite and/or viral infections.
566:(i.e., a system of proteins the increases the ability of antibodies and phagocytic cells to clear infecting microbes) and thereby increases an individual susceptibility to acquire 353:), further studies of less severe immune disorders, and analyses of multiple tissues in individuals that may have carry the dysfunctional gene in some but not their tissues (see 342: 1131:
Darmawan D, Raychaudhuri S, Lakshminrusimha S, Dimitriades VR (July 2024). "Hypogammaglobulinemia in neonates: illustrative cases and review of the literature".
467:(low levels of the circles indicate that the T cells have not matured); less severe forms of the combined immunodeficiencies are also included in this category. 112:
or other changes in any part of a gene that causes it to be dysfunctional.) Depending on the gene involved, this dysfunction may induce the development of an:
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Cheng J, Dávila Saldaña BJ, Chandrakasan S, Keller M (September 2024). "Pediatric lymphoproliferative disorders associated with inborn errors of immunity".
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Complement deficiencies consisting of 36 defective genes causing 30 diseases. These diseases involve decreases in the levels of a component protein in the
1736: 510:-induced immunity disorders. (About 50% of all five-year-old children and 90% of adults have evidence of previous infection with this virus; see 846:"Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers" 1254:"Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee" 762:"Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee" 811:
Clinical Microbiology and Infection : The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
283:, gene. The product of this gene, the BTK protein, contributes indirectly to promoting the production of all the antibody subtypes, i.e., 108:
causes increases in the susceptibility of individuals to develop a dysfunction in their immune system. (As used here, mutations include
635: 503: 311: 306:(PID), i.e., immune deficiencies that are present at birth and not caused by secondary factors such as other diseases or exposure to 610: 1363:
Palva T, Lehtinen T (December 1987). "Pneumococcal antigens and endotoxin in effusions from patients with secretory otitis media".
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Cellular and hormonal immunodeficiencies consisting of 66 defective genes causing 58 different diseases. These diseases include
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and characterized as an IEI, occurs in about 1 per 379,000 live births. It is also termed Bruton's agammaglobulinemia and the
326:(i.e., IEM) are a group of about 1700 disorders caused by a mutation in any one of about 1500 genes that causes a defect in a 1517:
Staels F, Collignon T, Betrains A, Gerbaux M, Willemsen M, Humblet-Baron S, Liston A, Vanderschueren S, Schrijvers R (2021).
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Congenital defects of phagocyte number or function consisting of 42 gene defects causing 35 diseases. These diseases include
1610:
Akalu YT, Bogunovic D (March 2024). "Inborn errors of immunity: an expanding universe of disease and genetic architecture".
1744: 219: 544:
Autoinflammatory disorders consisting of 56 defective genes causing 59 diseases. These diseases include various types of
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The International Union of Immunological Societies (2022) has classified IEI disorders into the following 10 categories:
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Predominantly antibody disorders consisting of 45 defective genes causing 51 diseases. These antibody disorders include
1740: 640: 475: 350: 323: 266: 211: 190: 275: 397:) or not expressed (termed non-penetrance) in males or females (these different expression patterns are also termed 318:(PIRDs; i.e., disorders of immunity characterized as excessive proliferations of lymphocytes and the development of 303: 1764: 545: 338: 207: 895:"Clinical and Immunologic Characteristics of Non-Hematologic Cancers in Patients with Inborn Errors of Immunity" 606: 116: 1685:"Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories" 502:
Diseases of immune dysregulation consisting of 52 defective genes causing 51 diseases. These diseases include
507: 238: 131: 844:
Hall MJ, Bernhisel R, Hughes E, Larson K, Rosenthal ET, Singh NA, Lancaster JM, Kurian AW (April 2021).
489: 425: 257: 893:
Delavari S, Wang Y, Moeini Shad T, Pashangzadeh S, Nazari F, Salami F, Abolhassani H (January 2023).
424:, i.e., caused by factors which regulate the expression of the IEI gene without changing this gene's 370: 120: 260:, i.e., his serum lacked detectible levels of circulating antibodies which attack infection-causing 581: 109: 145:
by causing a malfunction in one of the various components of the immune system that combat these
127: 596:
due to the failure of the bone marrow to produce sufficient level of one or more of these cells.
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that metabolizes proteins, fats, or carbohydrates or that impairs the function of a subcellular
1733:"About 90% of adults have antibodies that show that they have a current or past EBV infection" 1714: 1665: 1627: 1589: 1550: 1473: 1434: 1380: 1342: 1291: 1273: 1233: 1184: 1148: 1113: 1086: 1032: 997: 962: 926: 875: 826: 791: 736: 694: 589: 563: 433: 354: 327: 195: 58: 27: 413:
exposure to environmental factors with modify the activity of the inherited IEI gene (termed
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BRUTON OC, APT L, GITLIN D, JANEWAY CA (November 1952). "Absence of serum gamma globulins".
1076: 1066: 1024: 989: 954: 916: 906: 865: 857: 818: 781: 773: 728: 684: 676: 618: 456: 1403:"Common metabolic disorder (inborn errors of metabolism) concerns in primary care practice" 585: 366: 199: 63: 1700: 365:
As with other human genes, an IEI gene may be defective because it is not expressed (see
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the presence of other genes which modify the activity of the inherited IEI gene (termed
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non-hematological cancers as well as hematological cancers by causing a mutation in the
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Journal of Perinatology : Official Journal of the California Perinatal Association
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Bone marrow failure disorders consisting of 44 defective genes that cause 43 cases of
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A human immune disease that would later be classified as an IEI was first defined by
139: 105: 506:
and defects that cause an increases in the susceptibility of individuals to develop
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of inborn errors of immunity consisting of 15 genes that cause 15 cases of various
389:). Individuals who do inherit an IEI gene may still not exhibit symptoms because: 378: 374: 319: 245: 1732: 719:
Gray PE, David C (June 2023). "Inborn Errors of Immunity and Autoimmune Disease".
482:(i.e., gene defects that alter the development and function of the immune system). 1661: 602: 525: 521: 386: 234: 230: 169: 165: 1623: 1585: 1469: 1327: 1269: 1219: 1180: 1144: 1071: 993: 958: 777: 732: 680: 302:
Impairments in the immune system's protective actions have been referred to as
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activity or may not be present in offspring depending on its location in the
1419: 911: 593: 567: 529: 382: 331: 307: 153: 146: 142: 70: 1718: 1669: 1631: 1593: 1554: 1477: 1438: 1346: 1311:"Primary immune regulatory disorders: Undiagnosed needles in the haystack?" 1295: 1237: 1188: 1152: 1117: 1090: 1055:"Too much of a good thing: a review of primary immune regulatory disorders" 1036: 1001: 966: 930: 879: 830: 795: 740: 698: 1384: 1028: 493: 181: 97: 479: 460: 1648:
Yu JE (February 2024). "New primary immunodeficiencies 2023 update".
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International Union of Immunological Societies classification of IEI
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hematological cancers by causing a mutation in any one of various
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Agana M, Frueh J, Kamboj M, Patel DR, Kanungo S (December 2018).
1204:"Agammaglobulinemia: from X-linked to Autosomal Forms of Disease" 622: 270: 160:
immune system that overreacts to otherwise harmless substances;
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Notarangelo LD, Bacchetta R, Casanova JL, Su HC (July 2020).
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The Journal of Allergy and Clinical Immunology. In Practice
584:. These disorders are losses in the levels of circulating 512:
Epstein–Barr virus–associated lymphoproliferative diseases
322:), are immune disorders similar to those in IEI. Finally, 1202:
Cardenas-Morales M, Hernandez-Trujillo VP (August 2022).
665:"Human inborn errors of immunity: An expanding universe" 1167:
Cell Transplantation for X-Linked Agammaglobulinemia".
1365:
International Journal of Pediatric Otorhinolaryngology
381:, or one of 46 remaining non-sex chromosomes (termed 273:
that when mutated causes this disease is termed the
256:, Dr. Bruton was surprised to find that the boy had 184:(i.e., genes with the potential to cause a cancer); 96:) are a heterogenous group of disorders in which a 79: 69: 57: 46: 38: 26: 21: 496:classes, and other types of antibody deficiencies. 1519:"Monogenic Adult-Onset Inborn Errors of Immunity" 320:immune responses against one's own normal tissues 241:, liver, skin, or more than one of these organs. 455:diseases that are associated with low levels of 1643: 1641: 1605: 1603: 1566: 1564: 1450: 1448: 1396: 1394: 1106:A.M.A. American Journal of Diseases of Children 1048: 1046: 1496:International Union of Immunological Societies 1358: 1356: 850:Cancer Prevention Research (Philadelphia, Pa.) 754: 752: 750: 714: 712: 710: 708: 658: 656: 492:, i.e., reductions in one or more of the four 343:International Union of Immunological Societies 1015:BRUTON OC (June 1952). "Agammaglobulinemia". 8: 1208:Clinical Reviews in Allergy & Immunology 1492:"Inborn Errors of Immunity Committee (IEI)" 1053:Tsilifis C, Slatter MA, Gennery AR (2023). 42:Newborns, children, and, uncommonly, adults 524:not caused by antibodies directed against 222:by causing the excessive proliferation of 18: 1708: 1544: 1534: 1428: 1418: 1336: 1326: 1285: 1227: 1080: 1070: 920: 910: 869: 785: 688: 164:lose of one or more types of circulating 1737:National Center for Infectious Diseases 652: 621:that occur after fertilization of an 7: 1701:10.1146/annurev-pathol-031920-101429 1683:Casanova JL, Abel L (January 2021). 393:the gene is under expressed (termed 1309:Flinn AM, Gennery AR (March 2022). 982:Clinical Immunology (Orlando, Fla.) 947:Clinical Immunology (Orlando, Fla.) 617:. These phenocopy cases are due to 316:primary immune regulatory disorders 636:List of primary immunodeficiencies 504:hemophagocytic lymphohistiocytosis 312:List of primary immunodeficiencies 83:Rare but becoming much more common 14: 1315:Orphanet Journal of Rare Diseases 611:chronic mucocutaneous candidiasis 609:diseases (i.e., PID) such as the 1747:from the original on 2016-08-08. 1407:Annals of Translational Medicine 465:T-cell receptor excision circles 453:severe combined immunodeficiency 130:by causing a malfunction in the 119:by causing a malfunction in the 349:using automated methods (e.g., 310:agents. The PID disorders (see 194:gene (these cancers are mainly 1574:Journal of Clinical Immunology 1258:Journal of Clinical Immunology 1169:Journal of Clinical Immunology 862:10.1158/1940-6207.CAPR-20-0448 766:Journal of Clinical Immunology 574:-forming bacterial infections. 210:of the breast; see cancers in 1: 1650:Current Opinion in Pediatrics 220:lymphoproliferative disorders 138:viral, bacterial, fungal, or 1662:10.1097/MOP.0000000000001315 1377:10.1016/0165-5876(87)90022-x 550:familial Mediterranean fever 168:by causing a failure of the 641:Inborn errors of metabolism 476:combined immunodeficiencies 351:massive parallel sequencing 324:inborn errors of metabolism 267:X-linked agammaglobulinemia 212:ATM serine/threonine kinase 191:ATM serine/threonine kinase 172:to produce the circulating 1786: 1689:Annual Review of Pathology 1624:10.1038/s41576-023-00656-z 1586:10.1007/s10875-022-01352-z 1470:10.1126/sciimmunol.adh0368 1328:10.1186/s13023-022-02249-1 1270:10.1007/s10875-019-00737-x 1220:10.1007/s12016-021-08870-5 1181:10.1007/s10875-023-01551-2 1145:10.1038/s41372-023-01766-6 1072:10.3389/fimmu.2023.1279201 994:10.1016/j.clim.2024.110332 959:10.1016/j.clim.2024.109896 778:10.1007/s10875-022-01289-3 733:10.1016/j.jaip.2023.04.018 681:10.1126/sciimmunol.abb1662 528:and functional defects in 304:primary immunodeficiencies 1536:10.3389/fimmu.2021.753978 823:10.1016/j.cmi.2022.07.021 546:autoinflammatory diseases 399:gender-related penetrance 339:World Health Organization 208:invasive ductal carcinoma 90:Inborn errors of immunity 22:Inborn errors of immunity 1612:Nature Reviews. Genetics 607:primary immunodeficiency 314:) and its subgroup, the 276:Bruton's tyrosine kinase 117:autoinflammatory disease 1770:Immune system disorders 1523:Frontiers in Immunology 1420:10.21037/atm.2018.12.34 1059:Frontiers in Immunology 912:10.3390/cancers15030764 415:environmental modifiers 361:Expression of IEI genes 239:gastrointestinal tract 132:adaptive immune system 100:in any one of various 1743:. 28 September 2020. 1572:Errors of Immunity". 490:hypogammaglobulinemia 430:epigenetic regulation 426:nucleic acid sequence 371:dominant or recessive 258:hypogammaglobulinemia 33:Clinical immunologist 1029:10.1542/peds.9.6.722 121:innate immune system 50:Defects in specific 582:Bone marrow failure 463:plus low levels of 459:protein-expressing 395:reduced penetrrance 214:gene defects); and 1458:Science Immunology 669:Science Immunology 508:Epstein–Barr virus 128:autoimmune disease 104:that regulate the 817:(11): 1441–1448. 619:somatic mutations 590:white blood cells 564:complement system 407:genetic modifiers 196:pancreatic cancer 87: 86: 59:Diagnostic method 16:Medical condition 1777: 1765:Medical genetics 1749: 1748: 1729: 1723: 1722: 1712: 1680: 1674: 1673: 1645: 1636: 1635: 1607: 1598: 1597: 1580:(7): 1508–1520. 1568: 1559: 1558: 1548: 1538: 1514: 1508: 1507: 1505: 1503: 1488: 1482: 1481: 1464:(98): eadh0368. 1452: 1443: 1442: 1432: 1422: 1398: 1389: 1388: 1360: 1351: 1350: 1340: 1330: 1306: 1300: 1299: 1289: 1248: 1242: 1241: 1231: 1199: 1193: 1192: 1175:(8): 1827–1839. 1163: 1157: 1156: 1128: 1122: 1121: 1101: 1095: 1094: 1084: 1074: 1050: 1041: 1040: 1012: 1006: 1005: 977: 971: 970: 941: 935: 934: 924: 914: 890: 884: 883: 873: 841: 835: 834: 806: 800: 799: 789: 772:(7): 1473–1507. 756: 745: 744: 727:(6): 1602–1622. 716: 703: 702: 692: 660: 154:allergic disease 19: 1785: 1784: 1780: 1779: 1778: 1776: 1775: 1774: 1755: 1754: 1753: 1752: 1731: 1730: 1726: 1682: 1681: 1677: 1647: 1646: 1639: 1609: 1608: 1601: 1570: 1569: 1562: 1516: 1515: 1511: 1501: 1499: 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158:hypersensitive 85: 84: 81: 77: 76: 73: 67: 66: 61: 55: 54: 48: 44: 43: 40: 36: 35: 30: 24: 23: 15: 13: 10: 9: 6: 4: 3: 2: 1782: 1771: 1768: 1766: 1763: 1762: 1760: 1746: 1742: 1738: 1734: 1728: 1725: 1720: 1716: 1711: 1706: 1702: 1698: 1694: 1690: 1686: 1679: 1676: 1671: 1667: 1663: 1659: 1655: 1651: 1644: 1642: 1638: 1633: 1629: 1625: 1621: 1617: 1613: 1606: 1604: 1600: 1595: 1591: 1587: 1583: 1579: 1575: 1567: 1565: 1561: 1556: 1552: 1547: 1542: 1537: 1532: 1528: 1524: 1520: 1513: 1510: 1497: 1493: 1487: 1484: 1479: 1475: 1471: 1467: 1463: 1459: 1451: 1449: 1445: 1440: 1436: 1431: 1426: 1421: 1416: 1412: 1408: 1404: 1397: 1395: 1391: 1386: 1382: 1378: 1374: 1370: 1366: 1359: 1357: 1353: 1348: 1344: 1339: 1334: 1329: 1324: 1320: 1316: 1312: 1305: 1302: 1297: 1293: 1288: 1283: 1279: 1275: 1271: 1267: 1263: 1259: 1255: 1247: 1244: 1239: 1235: 1230: 1225: 1221: 1217: 1213: 1209: 1205: 1198: 1195: 1190: 1186: 1182: 1178: 1174: 1170: 1162: 1159: 1154: 1150: 1146: 1142: 1138: 1134: 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358: 356: 352: 348: 344: 340: 337:In 1973, the 335: 333: 329: 325: 321: 317: 313: 309: 305: 300: 298: 294: 290: 286: 282: 278: 277: 272: 268: 263: 259: 255: 251: 247: 242: 240: 236: 232: 229: 225: 221: 217: 213: 209: 205: 201: 197: 193: 192: 187: 183: 179: 175: 171: 167: 163: 159: 156:by causing a 155: 152: 148: 144: 141: 140:mycobacterial 137: 133: 129: 126: 122: 118: 115: 111: 107: 106:immune system 103: 99: 95: 91: 82: 78: 74: 72: 68: 65: 62: 60: 56: 53: 49: 45: 41: 37: 34: 31: 29: 25: 20: 1727: 1692: 1688: 1678: 1653: 1649: 1615: 1611: 1577: 1573: 1526: 1522: 1512: 1500:. 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US 254:serum 102:genes 52:genes 1715:PMID 1666:PMID 1628:PMID 1590:PMID 1551:PMID 1504:2020 1474:PMID 1435:PMID 1381:PMID 1343:PMID 1292:PMID 1274:ISSN 1234:PMID 1185:PMID 1149:PMID 1114:PMID 1087:PMID 1033:PMID 998:PMID 963:PMID 927:PMID 876:PMID 827:PMID 792:PMID 737:PMID 695:PMID 623:ovum 600:10). 570:and 552:and 271:gene 206:and 1741:CDC 1705:PMC 1697:doi 1658:doi 1620:doi 1582:doi 1541:PMC 1531:doi 1466:doi 1425:PMC 1415:doi 1373:doi 1333:PMC 1323:doi 1282:PMC 1266:doi 1224:PMC 1216:doi 1177:doi 1141:doi 1077:PMC 1067:doi 1025:doi 990:doi 986:266 955:doi 951:259 917:PMC 907:doi 866:PMC 858:doi 819:doi 782:PMC 774:doi 729:doi 685:PMC 677:doi 578:9). 572:pus 560:8). 542:7). 536:6). 518:5). 500:4). 486:3). 471:2). 457:CD3 449:1). 432:). 409:), 401:), 299:. 297:IgE 293:IgM 289:IgA 285:IgG 281:BKT 226:or 94:IEI 1761:: 1735:. 1713:. 1703:. 1693:16 1691:. 1687:. 1664:. 1654:36 1652:. 1640:^ 1626:. 1616:25 1614:. 1602:^ 1588:. 1578:42 1576:. 1563:^ 1549:. 1539:. 1527:12 1525:. 1521:. 1494:. 1472:. 1460:. 1447:^ 1433:. 1423:. 1409:. 1405:. 1393:^ 1379:. 1369:14 1367:. 1355:^ 1341:. 1331:. 1319:17 1317:. 1313:. 1290:. 1280:. 1272:. 1262:40 1260:. 1256:. 1232:. 1222:. 1212:63 1210:. 1206:. 1183:. 1173:43 1171:. 1147:. 1137:44 1135:. 1110:84 1108:. 1085:. 1075:. 1063:14 1061:. 1057:. 1045:^ 1031:. 1019:. 996:. 984:. 961:. 949:. 925:. 915:. 903:15 901:. 897:. 874:. 864:. 854:14 852:. 848:. 825:. 815:28 813:. 790:. 780:. 770:42 768:. 764:. 749:^ 735:. 725:11 723:. 707:^ 693:. 683:. 671:. 667:. 655:^ 588:, 514:). 419:d) 411:c) 403:b) 391:a) 377:, 291:, 287:, 237:, 216:h) 202:, 198:, 186:g) 178:f) 162:e) 151:d) 149:; 136:c) 134:; 125:b) 123:; 114:a) 1721:. 1699:: 1672:. 1660:: 1634:. 1622:: 1596:. 1584:: 1557:. 1533:: 1506:. 1480:. 1468:: 1462:9 1441:. 1417:: 1411:6 1387:. 1375:: 1349:. 1325:: 1298:. 1268:: 1240:. 1218:: 1191:. 1179:: 1155:. 1143:: 1120:. 1093:. 1069:: 1039:. 1027:: 1021:9 1004:. 992:: 969:. 957:: 933:. 909:: 882:. 860:: 833:. 821:: 798:. 776:: 743:. 731:: 701:. 679:: 673:5 556:. 92:(

Index

Specialty
Clinical immunologist
genes
Diagnostic method
Genetic testing
Prognosis
mutation
genes
immune system
deletions
autoinflammatory disease
innate immune system
autoimmune disease
adaptive immune system
mycobacterial
infection
pathogens
allergic disease
hypersensitive
blood cells
bone marrow
blood cell
oncogenes
ATM serine/threonine kinase
pancreatic cancer
prostate cancer
stomach cancer
invasive ductal carcinoma
ATM serine/threonine kinase
lymphoproliferative disorders

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