Severe combined immunodeficiency - Wikipedia

Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development ... Severecombinedimmunodeficiency FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch MedicalconditionSevereCombinedImmuneDeficiencyOthernamesAlymphocytosis,Glanzmann–Rinikersyndrome,Severemixedimmunodeficiencysyndrome,andThymicalymphoplasia[1]DavidVetter,achildbornin1971withseverecombinedimmunodeficiency(SCID).SpecialtyImmunology TreatmentBonemarrowtransplantationandprophylaxisagainstinfectionMedicationIVIG,genetherapyFrequency1in50,000to100,000(X-linkedform) Severecombinedimmunodeficiency(SCID),alsoknownasSwiss-typeagammaglobulinemia,isararegeneticdisordercharacterizedbythedisturbeddevelopmentoffunctionalTcellsandBcellscausedbynumerousgeneticmutationsthatresultindifferingclinicalpresentations.[2]SCIDinvolvesdefectiveantibodyresponseduetoeitherdirectinvolvementwithBlymphocytesorthroughimproperBlymphocyteactivationduetonon-functionalT-helpercells.[3]Consequently,both"arms"(BcellsandTcells)oftheadaptiveimmunesystemareimpairedduetoadefectinoneofseveralpossiblegenes.SCIDisthemostsevereformofprimaryimmunodeficiencies,[4]andtherearenowatleastninedifferentknowngenesinwhichmutationsleadtoaformofSCID.[5]Itisalsoknownasthebubbleboydiseaseandbubblebabydiseasebecauseitsvictimsareextremelyvulnerabletoinfectiousdiseasesandsomeofthem,suchasDavidVetter,havebecomefamousforlivinginasterileenvironment.SCIDistheresultofanimmunesystemsohighlycompromisedthatitisconsideredalmostabsent. SCIDpatientsareusuallyaffectedbyseverebacterial,viral,orfungalinfectionsearlyinlifeandoftenpresentwithinterstitiallungdisease,chronicdiarrhea,andfailuretothrive.[3]Earinfections,recurrentPneumocystisjirovecii(previouslycarinii)pneumonia,andprofuseoralcandidiasiscommonlyoccur.Thesebabies,ifuntreated,usuallydiewithinoneyearduetosevere,recurrentinfectionsunlesstheyhaveundergonesuccessfulhematopoieticstemcelltransplantationorgenetherapyinclinicaltrials.[6] Contents 1Classification 2Diagnosis 2.1Newbornscreening 3Treatment 4Epidemiology 5SCIDinanimals 6Seealso 7References 8Furtherreading 9Externallinks Classification[edit] Type Description X-linkedseverecombinedimmunodeficiency MostcasesofSCIDareduetomutationsintheIL2RGgeneencodingthecommongammachain(γc)(CD132),aproteinthatissharedbythereceptorsforinterleukinsIL-2,IL-4,IL-7,IL-9,IL-15andIL-21.TheseinterleukinsandtheirreceptorsareinvolvedinthedevelopmentanddifferentiationofTandBcells.Becausethecommongammachainissharedbymanyinterleukinreceptors,mutationsthatresultinanon-functionalcommongammachaincausewidespreaddefectsininterleukinsignalling.Theresultisanearcompletefailureoftheimmunesystemtodevelopandfunction,withloworabsentTcellsandNKcellsandnon-functionalBcells.ThecommongammachainisencodedbythegeneIL-2receptorgamma,orIL-2Rγ,whichislocatedontheX-chromosome.Forthisreason,immunodeficiencycausedbymutationsinIL-2RγisknownasX-linkedseverecombinedimmunodeficiency.TheconditionisinheritedinanX-linkedrecessivepattern. Adenosinedeaminasedeficiency ThesecondmostcommonformofSCIDafterX-SCIDiscausedbyadefectiveenzyme,adenosinedeaminase(ADA),necessaryforthebreakdownofpurines.LackofADAcausesaccumulationofdATP.Thismetabolitewillinhibittheactivityofribonucleotidereductase,theenzymethatreducesribonucleotidestogeneratedeoxyribonucleotides.TheeffectivenessoftheimmunesystemdependsuponlymphocyteproliferationandhencedNTPsynthesis.Withoutfunctionalribonucleotidereductase,lymphocyteproliferationisinhibitedandtheimmunesystemiscompromised. Purinenucleosidephosphorylasedeficiency Anautosomalrecessivedisorderinvolvingmutationsofthepurinenucleosidephosphorylase(PNP)gene.PNPisakeyenzymeinthepurinesalvagepathway.ImpairmentofthisenzymecauseselevateddGTPlevelsresultinginT-celltoxicityanddeficiency. Reticulardysgenesis Inabilityofgranulocyteprecursorstoformgranulessecondarytomitochondrialadenylatekinase2(AK2)malfunction. Omennsyndrome ThemanufactureofimmunoglobulinsrequiresrecombinaseenzymesderivedfromtherecombinationactivatinggenesRAG-1andRAG-2.TheseenzymesareinvolvedinthefirststageofV(D)Jrecombination,theprocessbywhichsegmentsofaBcellorTcell'sDNAarerearrangedtocreateanewTcellreceptororBcellreceptor(and,intheBcell'scase,thetemplateforantibodies).CertainmutationsoftheRAG-1orRAG-2genespreventV(D)Jrecombination,causingSCID.[7] Barelymphocytesyndrome Type1:MHCclassIisnotexpressedonthecellsurface.ThedefectiscausedbydefectiveTAPproteins,nottheMHC-Iprotein. Type2:MHCclassIIisnotexpressedonthecellsurfaceofallantigenpresentingcells.Autosomalrecessive.TheMHC-IIgeneregulatoryproteinsarewhatisaltered,nottheMHC-IIproteinitself. JAK3 Januskinase-3(JAK3)isanenzymethatmediatestransductiondownstreamoftheγcsignal.MutationofitsgenecausesSCID.[8] DCLRE1C DCLRE1C"Artemis"isagenerequiredforDNArepairandV(D)Jrecombination.Arecessiveloss-of-functionmutationfoundtheNavajoandApachepopulationcausesSCIDandradiationintolerance.[9][10] Diagnosis[edit] EarlydiagnosisofSCIDisusuallydifficultduetotheneedforadvancedscreeningtechniques.SeveralsymptomsmayindicateapossibilityofSCIDinachild,suchasafamilyhistoryofinfantdeath,chroniccoughs,hyperinflatedlungs,andpersistentinfections.AfullbloodlymphocytecountisoftenconsideredareliablemannerofdiagnosingSCID,buthigherlymphocytecountsinchildhoodmayinfluenceresults.ClinicaldiagnosisbasedongeneticdefectsisalsoapossiblediagnosticprocedurethathasbeenimplementedintheUK.[11] SomeSCIDcanbedetectedbysequencingfetalDNAifaknownhistoryofthediseaseexists.Otherwise,SCIDisnotdiagnoseduntilaboutsixmonthsofage,usuallyindicatedbyrecurrentinfections.Thedelayindetectionisbecausenewbornscarrytheirmother'santibodiesforthefirstfewweeksoflifeandSCIDbabieslooknormal.[citationneeded] Newbornscreening[edit] SeveralcountriestestallnewbornsforSCIDasapartofroutinenewbornscreening.AllstatesintheU.S.[12]areperformingscreeningforSCIDinnewbornsusingreal-timequantitativePCRtomeasuretheconcentrationofT-cellreceptorexcisioncircles.[13]UnitedKingdomintendstointroducenewbornscreeningforSCIDinSeptember2021.[14] Treatment[edit] ThemostcommontreatmentforSCIDisbonemarrowtransplantation,whichhasbeenverysuccessfulusingeitheramatchedrelatedorunrelateddonor,orahalf-matcheddonor,whowouldbeeitherparent.Thehalf-matchedtypeoftransplantiscalledhaploidentical.HaploidenticalbonemarrowtransplantsrequirethedonormarrowtobedepletedofallmatureTcellstoavoidtheoccurrenceofgraft-versus-hostdisease(GVHD).[15]Consequently,afunctionalimmunesystemtakeslongertodevelopinapatientwhoreceivesahaploidenticalbonemarrowtransplantcomparedtoapatientreceivingamatchedtransplant.ThefirstreportedcaseofsuccessfultransplantwasaSpanishchildpatientwhowasinternedinMemorialSloanKetteringCancerCenterin1982,inNewYorkCity.[15]DavidVetter,theoriginal"bubbleboy",hadoneofthefirsttransplantationsalso,buteventuallydiedbecauseofanunscreenedvirus,Epstein-Barr(testswerenotavailableatthetime),inhisnewlytransplantedbonemarrowfromhissister,anunmatchedbonemarrowdonor.Today,transplantsdoneinthefirstthreemonthsoflifehaveahighsuccessrate.Physicianshavealsohadsomesuccesswithinuterotransplantsdonebeforethechildisbornandalsobyusingcordbloodwhichisrichinstemcells.Inuterotransplantsallowforthefetustodevelopafunctionalimmunesysteminthesterileenvironmentoftheuterus;[16]howevercomplicationssuchasGVHDwouldbedifficulttodetectortreatiftheyweretooccur.[17] Morerecentlygenetherapyhasbeenattemptedasanalternativetothebonemarrowtransplant.TransductionofthemissinggenetohematopoieticstemcellsusingviralvectorsisbeingtestedinADASCIDandX-linkedSCID.In1990,four-year-oldAshanthiDeSilvabecamethefirstpatienttoundergosuccessfulgenetherapy.ResearcherscollectedsamplesofDeSilva'sblood,isolatedsomeofherwhitebloodcells,andusedaretrovirustoinsertahealthyadenosinedeaminase(ADA)geneintothem.Thesecellsweretheninjectedbackintoherbody,andbegantoexpressanormalenzyme.This,augmentedbyweeklyinjectionsofADA,correctedherdeficiency.However,theconcurrenttreatmentofADAinjectionsmayimpairthesuccessofgenetherapy,sincetransducedcellswillhavenoselectiveadvantagetoproliferateifuntransducedcellscansurviveinthepresenceoftheinjectedADA.[18] DavidVetterinsidehisprotective"bubble." In2000,agenetherapy"success"resultedinSCIDpatientswithafunctionalimmunesystem.Thesetrialswerestoppedwhenitwasdiscoveredthattwooftenpatientsinonetrialhaddevelopedleukemiaresultingfromtheinsertionofthegene-carryingretrovirusnearanoncogene.In2007,fourofthetenpatientshavedevelopedleukemias.[19]Workaimedatimprovinggenetherapyisnowfocusingonmodifyingtheviralvectortoreducethelikelihoodofoncogenesisandusingzinc-fingernucleasestofurthertargetgeneinsertion.[20]NoleukemiacaseshaveyetbeenseenintrialsofADA-SCID,whichdoesnotinvolvethegammacgenethatmaybeoncogenicwhenexpressedbyaretrovirus. FromthetreatmentsofAshanthiDeSilvain1990whichisconsideredgenetherapy'sfirstsuccessuntil2014around60patientsweretreatedforeitherADA-SCIDorX-SCID[21]usingretrovirusesvectorsbutaspreviouslymentionedtheoccurrenceofcasesdevelopingleukemiaforcedtomakechangestoimprovesafety,[22]morerecentlyin2019anewmethodusinganalteredversionoftheHIVvirusasalentivirusvectorwasreportedinthetreatmentof8childrenwithX-SCID,[23][24][25][6]andin2021thesamemethodwasusedin50childrenwithADA-SCIDobtainingpositiveresultsin48ofthem.[26][27][28] Therearealsosomenon-curativemethodsfortreatingSCID.Reverseisolationinvolvestheuseoflaminarairflowandmechanicalbarriers(toavoidphysicalcontactwithothers)toisolatethepatientfromanyharmfulpathogenspresentintheexternalenvironment.[29]Anon-curativetreatmentforpatientswithADA-SCIDisenzymereplacementtherapy,inwhichthepatientisinjectedwithpolyethyleneglycol-coupledadenosinedeaminase(PEG-ADA)whichmetabolizesthetoxicsubstratesoftheADAenzymeandpreventstheiraccumulation.[18]TreatmentwithPEG-ADAmaybeusedtorestoreTcellfunctionintheshortterm,enoughtoclearanyexistinginfectionsbeforeproceedingwithcurativetreatmentsuchasabonemarrowtransplant.[30] Epidemiology[edit] ThemostcommonlyquotedfigurefortheprevalenceofSCIDisaround1in100,000births,althoughthisisregardedbysometobeanunderestimateofthetrueprevalence;[31]someestimatespredictthattheprevalencerateisashighas1in50,000livebirths.[3]Afigureofabout1in65,000livebirthshasbeenreportedforAustralia.[32] DuetotheparticulargeneticnatureofSCID,ahigherprevalencemaybefoundincertainregionsandassociatedcultureswherehigherratesofconsanguineousmatingoccur.[33]AMoroccanstudyreportedthatconsanguineousparentingwasobservedin75%ofthefamiliesofMoroccanSCIDpatients.[34] Recentstudiesindicatethatoneinevery2,500childrenintheNavajopopulationinheritseverecombinedimmunodeficiency.ThisconditionisasignificantcauseofillnessanddeathamongNavajochildren.[9]OngoingresearchrevealsasimilargeneticpatternamongtherelatedApachepeople.[10] SCIDinanimals[edit] Mainarticle:Severecombinedimmunodeficiency(non-human) SCIDmicewereandstillareusedindisease,vaccine,andtransplantresearch;especiallyasanimalmodelsfortestingthesafetyofnewvaccinesortherapeuticagentsinpeoplewithweakenedimmunesystem. Recessivegenewithclinicalsignssimilartothehumancondition,alsoaffectstheArabianhorse.Inhorses,theconditionremainsafataldisease,astheanimalinevitablysuccumbstoanopportunisticinfectionwithinthefirstfourtosixmonthsoflife.[35]However,carriers,whothemselvesarenotaffectedbythedisease,canbedetectedwithaDNAtest.Thuscarefulbreedingpracticescanavoidtheriskofanaffectedfoalbeingproduced.[36] Anotheranimalwithwell-characterizedSCIDpathologyisthedog.Therearetwoknownforms,anX-linkedSCIDinBassetHoundsthathassimilarontologytoX-SCIDinhumans[37]andanautosomalrecessiveformseeninonelineofJackRussellTerriersthatissimilartoSCIDinArabianhorsesandmice.[38] SCIDmicealsoserveasausefulanimalmodelinthestudyofthehumanimmunesystemanditsinteractionswithdisease,infections,andcancer.[39]Forexample,normalstrainsofmicecanbelethallyirradiated,killingallrapidlydividingcells.ThesemicethenreceivebonemarrowtransplantationfromSCIDdonors,allowingengraftmentofhumanperipheralbloodmononuclearcells(PBMC)tooccur.ThismethodcanbeusedtostudywhetherTcell-lackingmicecanperformhematopoiesisafterreceivinghumanPBMC.[40] Seealso[edit] DavidVetter AishaChaudhary Listofcutaneousconditions Listofradiographicfindingsassociatedwithcutaneousconditions References[edit] ^Rapini,RonaldP.;Bolognia,JeanL.;Jorizzo,JosephL.(2007).Dermatology:2-VolumeSet.St.Louis:Mosby.ISBN 978-1-4160-2999-1. ^BurgM,GenneryAR(2011)."Educationalpaper:Theexpandingclinicalandimmunologicalspectrumofseverecombinedimmunodeficiency".EurJPediatr.170(5):561–571.doi:10.1007/s00431-011-1452-3.PMC 3078321.PMID 21479529. ^abcAlojG,GiardanoG,ValentinoL,MaioF,GalloV,EspositoT,NaddeiR,CirilloE,PignataC(2012)."Severecombinedimmunodeficiencies:NewandOldScenarios".IntRevImmunol.31(1):43–65.doi:10.3109/08830185.2011.644607.PMID 22251007.S2CID 24088244. ^Cavazanna-CalvoM,Hacein-BeyS,YatesF,deVillartayJP,LeDeistF,FischerA(2001)."Genetherapyofseverecombinedimmunodeficiencies".JGeneMed.3(3):201–206.doi:10.1002/1521-2254(200105/06)3:3<201::AID-JGM195>3.0.CO;2-Z.PMID 11437325. ^BuckleyR(2003)."Moleculardefectsinhumanseverecombinedimmunodeficiencyandapproachestoimmunereconstitution".AnnuRevImmunol.22:625–655.doi:10.1146/annurev.immunol.22.012703.104614.PMID 15032591. ^abRohr,Karen(2019-04-17)."Genetherapyrestoresimmunityininfantswithrareimmunodeficiencydisease".NationalInstitutesofHealth(NIH).Retrieved2020-06-04. ^HaqIJ,SteinbergLJ,HoenigM,et al.(2007)."GvHD-associatedcytokinepolymorphismsdonotassociatewithOmennsyndromeratherthanT-B-SCIDinpatientswithdefectsinRAGgenes".Clin.Immunol.124(2):165–9.doi:10.1016/j.clim.2007.04.013.PMID 17572155. ^PesuM,CandottiF,HusaM,HofmannSR,NotarangeloLD,O'SheaJJ(2005)."Jak3,severecombinedimmunodeficiency,andanewclassofimmunosuppressivedrugs".Immunol.Rev.203:127–42.doi:10.1111/j.0105-2896.2005.00220.x.PMID 15661026.S2CID 20684919. ^ab"NewsFromIndianCountry-Arareandonce-bafflingdiseaseforcesNavajoparentstocope".Archivedfromtheoriginalon19April2012.Retrieved2008-03-01. ^abLiL,MoshousD,ZhouY,et al.(2002)."AfoundermutationinArtemis,anSNM1-likeprotein,causesSCIDinAthabascan-speakingNativeAmericans".J.Immunol.168(12):6323–9.doi:10.4049/jimmunol.168.12.6323.PMID 12055248. ^Gennery,A;Cant,A(March2001)."Diagnosisofseverecombinedimmunodeficiency".JClinPathol.54(3):191–195.doi:10.1136/jcp.54.3.191.PMC 1731376.PMID 11253129. ^vanderBurg,Mirjam;Mahlaoui,Nizar;Gaspar,HubertBobby;Pai,Sung-Yun(2019-09-18)."UniversalNewbornScreeningforSevereCombinedImmunodeficiency(SCID)".FrontiersinPediatrics.7:373.doi:10.3389/fped.2019.00373.ISSN 2296-2360.PMC 6759820.PMID 31620409. ^"NationalNewbornScreeningStatusReport"(PDF). ^"NewstartdateforNHSSCIDscreeningevaluationinEngland-PHEScreening".phescreening.blog.gov.uk.Retrieved2021-06-21. ^abChinenJ,BuckleyRH(2010)."Transplantationimmunology:solidorganandbonemarrow".J.AllergyClin.Immunol.125(2Suppl2):S324-35. ^Vickers,PeterS.(2009).Severecombinedimmunedeficiency:earlyhospitalisationandisolation.HobokenNJ:JohnWiley&Sons,29-47.ISBN 978-0-470-74557-1. ^BuckleyRH(2004)."Moleculardefectsinhumanseverecombinedimmunodeficiencyandapproachestoimmunereconstitution".Annu.Rev.Immunol.22(1):625–655.doi:10.1146/annurev.immunol.22.012703.104614.PMID 15032591. ^abFischerA,Hacein-BeyS,Cavazzana-CalvoM(2002)."Genetherapyofseverecombinedimmunodeficiencies".NatRevImmunol.2(8):615–621.doi:10.1038/nri859.PMID 12154380.S2CID 39791932. ^PressreleasefromtheEuropeanSocietyofGeneTherapy ^Cavazzana-CalvoM,FischerA(2007)."Genetherapyforseverecombinedimmunodeficiency:arewethereyet?"".J.Clin.Invest.117(6):1456–1465.doi:10.1172/jci30953.PMC 1878528.PMID 17549248. ^Cavazzana-Calvo,Marina;Fischer,Alain;Hacein-Bey-Abina,Salima;Aiuti,Alessandro(October2012)."Genetherapyforprimaryimmunodeficiencies:Part1".CurrentOpinioninImmunology.24(5):580–584.doi:10.1016/j.coi.2012.08.008.ISSN 1879-0372.PMID 22981681. ^"WhyGeneTherapyCausedLeukemiaInSome'BoyInTheBubbleSyndrome'Patients".ScienceDaily.Retrieved2021-07-19. ^Mamcarz,Ewelina;Zhou,Sheng;Lockey,Timothy;Abdelsamed,Hossam;Cross,ShaneJ.;Kang,Guolian;Ma,Zhijun;Condori,Jose;Dowdy,Jola;Triplett,Brandon;Li,Chen(2019-04-18)."LentiviralGeneTherapyCombinedwithLow-DoseBusulfaninInfantswithSCID-X1".NewEnglandJournalofMedicine.380(16):1525–1534.doi:10.1056/NEJMoa1815408.ISSN 0028-4793.PMC 6636624.PMID 30995372. ^"HIVusedtocure'bubbleboy'disease".BBCNews.2019-04-17.Retrieved2021-07-19. ^Pittman,JessicaRavitz,JohnDavid."TheseScientistsMayHaveFoundaCurefor'BubbleBoy'Disease".SmithsonianMagazine.Retrieved2021-07-19. ^Kohn,DonaldB.;Booth,Claire;Shaw,KitL.;Xu-Bayford,Jinhua;Garabedian,Elizabeth;Trevisan,Valentina;Carbonaro-Sarracino,DeniseA.;Soni,Kajal;Terrazas,Dayna;Snell,Katie;Ikeda,Alan(2021-05-27)."AutologousExVivoLentiviralGeneTherapyforAdenosineDeaminaseDeficiency".NewEnglandJournalofMedicine.384(21):2002–2013.doi:10.1056/NEJMoa2027675.ISSN 0028-4793.PMC 8240285.PMID 33974366. ^says,Chris(2021-05-11)."AIDSvirususedingenetherapytofix'bubblebaby'disease".STAT.Retrieved2021-07-19. ^"Genetherapyrestoresimmunefunctioninchildrenwithrareimmunodeficiency".NationalInstitutesofHealth(NIH).2021-05-11.Retrieved2021-07-19. ^TamaroffMH,NirY,StrakerN(1986)."Childrenrearedinareverseisolationenvironment:effectsoncognitiveandemotionaldevelopment".J.AutismDev.Disord.16(4):415–424.doi:10.1007/bf01531708.PMID 3804957.S2CID 30045420. ^VanderBurg,M;Gennery,AR(2011)."Educationalpaper.Theexpandingclinicalandimmunologicalspectrumofseverecombinedimmunodeficiency".Eur.J.Pediatr.170(5):561–571.doi:10.1007/s00431-011-1452-3.PMC 3078321.PMID 21479529. ^"NewbornScreeningforPrimaryImmunodeficiencyDisease". ^YeeA,DeRavinSS,ElliottE,ZieglerJB(2008)."Severecombinedimmunodeficiency:Anationalsurveillancestudy".PediatrAllergyImmunol.19(4):298–302.doi:10.1111/j.1399-3038.2007.00646.x.PMID 18221464.S2CID 26379956. ^YeganehM,HeidarzadeM,PourpakZ,ParvanehN,RezaeiN,GharagozlouM,MovahedM,ShabestariMS,MamishiS,AghamohammadiA,MoinM(2008)."Severecombinedimmunodeficiency:Acohortof40patients".PediatrAllergyImmunol.19(4):303–306.doi:10.1111/j.1399-3038.2007.00647.x.PMID 18093084.S2CID 29466366. ^El-MaataouiO,AilalF,NaamaneH,BenhsaienI,JeddaneL,FarouqiB,BenslimaneA,JilaliN,OudghiriM,BousfihaA(2011)."ImmunophenotypingofseverecombinedimmunodeficiencyinMorocco".IBSJSci.26(4):161–164.doi:10.1016/j.immbio.2011.05.002. ^FOAL.org,anorganizationpromotingresearchintogeneticlethaldiseasesinhorse ^"TheNewDNATestforSevereCombinedImmunodeficiency(SCID)inArabianHorses" ^HenthornPS,SombergRL,FimianiVM,PuckJM,PattersonDF,FelsburgPJ(1994)."IL-2RgammagenemicrodeletiondemonstratesthatcanineX-linkedseverecombinedimmunodeficiencyisahomologueofthehumandisease".Genomics.23(1):69–74.doi:10.1006/geno.1994.1460.PMID 7829104. ^PerrymanLE(2004)."Molecularpathologyofseverecombinedimmunodeficiencyinmice,horses,anddogs".Vet.Pathol.41(2):95–100.doi:10.1354/vp.41-2-95.PMID 15017021.S2CID 38273912. ^Owen,Judith;Punt,Jenni(2013).KubyImmunology.NewYork:W.H.FreemanandCompany. ^"CONVERSIONOFNORMALRATSINTOSCID-LIKEANIMALSBYMEANSOFBONEMARROWTRANSPLANTATIONFROMSCIDDONORSALLOWSENGRAFTMENTOFHUMANPERIPHERALBLOODMONONUCLEARCELLS" Furtherreading[edit] BuckleyRH(2004)."Moleculardefectsinhumanseverecombinedimmunodeficiencyandapproachestoimmunereconstitution".AnnuRevImmunol.22:625–55.doi:10.1146/annurev.immunol.22.012703.104614.PMID 15032591. ChinenJ,PuckJM(2004)."Successesandrisksofgenetherapyinprimaryimmunodeficiencies".JAllergyClinImmunol.113(4):595–603,quiz604.doi:10.1016/j.jaci.2004.01.765.PMID 15100660. ChurchAC(2002)."X-linkedseverecombinedimmunodeficiency".HospMed.63(11):676–80.doi:10.12968/hosp.2002.63.11.1914.PMID 12474613. GenneryAR,CantAJ(2001)."Diagnosisofseverecombinedimmunodeficiency".JClinPathol.54(3):191–5.doi:10.1136/jcp.54.3.191.PMC 1731376.PMID 11253129. Externallinks[edit] LearningAboutSevereCombinedImmunodeficiency(SCID)NIH ClassificationDICD-10:D81.0-D81.2ICD-9-CM:279.2MeSH:D016511DiseasesDB:11978ExternalresourceseMedicine:med/2214Orphanet:183660 vteLymphoidandcomplementdisorderscausingimmunodeficiencyPrimaryAntibody/humoral(B)Hypogammaglobulinemia X-linkedagammaglobulinemia Transienthypogammaglobulinemiaofinfancy Dysgammaglobulinemia IgAdeficiency IgGdeficiency IgMdeficiency HyperIgMsyndrome(1 2 3 4 5) Wiskott–Aldrichsyndrome Hyper-IgEsyndrome Other Commonvariableimmunodeficiency ICFsyndrome Tcelldeficiency(T) thymichypoplasia:hypoparathyroid(DiGeorge'ssyndrome) euparathyroid(Nezelofsyndrome Ataxia–telangiectasia) peripheral:Purinenucleosidephosphorylasedeficiency HyperIgMsyndrome(1) Severecombined(B+T) x-linked:X-SCIDautosomal:Adenosinedeaminasedeficiency Omennsyndrome ZAP70deficiency Barelymphocytesyndrome Acquired HIV/AIDS Leukopenia:Lymphocytopenia IdiopathicCD4+lymphocytopenia Complementdeficiency C1-inhibitor(Angioedema/Hereditaryangioedema) Complement2deficiency/Complement4deficiency MBLdeficiency Properdindeficiency Complement3deficiency Terminalcomplementpathwaydeficiency Paroxysmalnocturnalhemoglobinuria Complementreceptordeficiency vteMetabolicdisease:DNAreplicationandDNArepair-deficiencydisorderDNAreplication Separation/initiation:RNASEH2A Aicardi–Goutièressyndrome4 Termination/telomerase:DKC1 Dyskeratosiscongenita DNArepairNucleotideexcisionrepair Cockaynesyndrome/DeSanctis–Cacchionesyndrome Thyminedimer Xerodermapigmentosum IBIDSsyndrome MSI/DNAmismatchrepair Hereditarynonpolyposiscolorectalcancer Muir–Torresyndrome Mismatchrepaircancersyndrome MRNcomplex Ataxiatelangiectasia Nijmegenbreakagesyndrome Other RecQhelicase Bloomsyndrome Wernersyndrome Rothmund–Thomsonsyndrome/Rapadilinosyndrome Fanconianemia Li-Fraumenisyndrome Severecombinedimmunodeficiency Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Severe_combined_immunodeficiency&oldid=1065723644" Categories:CombinedTandB–cellimmunodeficienciesDNAreplicationandrepair-deficiencydisordersGeneticdisordersbysystemNoninfectiousimmunodeficiency-relatedcutaneousconditionsRarediseasesHiddencategories:ArticleswithshortdescriptionShortdescriptionisdifferentfromWikidataAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromSeptember2020 Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Languages العربيةBosanskiCatalàČeštinaDeutschEestiΕλληνικάEspañolFrançaisGaeilgeBahasaIndonesiaItalianoעבריתBahasaMelayuNederlandsPolskiРусскийСрпски/srpskiSvenskaไทย中文 Editlinks