文档介绍：该【Tuberculosis Risk Stratification of Psoriatic Patients Before Anti-TNF-α Treatment 2021 Farida Benhadou 】是由【玉柱儿】上传分享，文档一共【10】页，该文档可以免费在线阅读，需要了解更多关于【Tuberculosis Risk Stratification of Psoriatic Patients Before Anti-TNF-α Treatment 2021 Farida Benhadou 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。ORIGINALRESEARCH
published:03June2021
doi:.672894
TuberculosisRiskStratification
ofPsoriaticPatientsBefore
Anti-TNF-aTreatment
FaridaBenhadou1,VioletteDirix2,FannyDomont2,FabienneWillaert1,AnneVanPraet2,
CamilleLocht3,Franc¸oiseMascart2*andVe´roniqueCorbière2
1DermatologyDepartment,HoˆpitalErasme,Universite´LibredeBruxelles(.),Brussels,Belgium,2Laboratoryof
VaccinologyandMucosalImmunity,Universite´LibredeBruxelles(.),Brussels,Belgium,,CNRS,Inserm,
CHULille,InstitutPasteurdeLille,U1019–UMR8204–CIIL-CenterforInfectionandImmunityofLille,Lille,France
Psoriasisisaskininflammatoryconditionforwhichsignificantprogresshasbeenmadeinits
infection(LTBI)ismandatorybeforestartingbiotherapythatisassociatedwithreactivation
,tuberculinskintests
(TST)and/orbloodinterferon-g-releaseassays(IGRA),liketheQuantiFERON(QFT),are
,14/49
Editedby:psoriaticpatientsprospectivelyincludedinthisstudywereidentifiedasLTBI(14TST+,
HazelMargueriteDockrell,≥+
UniversityofLondon,UnitedKingdomindurationsize10mm,8QFT),and7/14receivedprophylacticanti-TBtreatment,the
Reviewedby:other7reportingpast-
VigneshRamachandran,challenged,weevaluatedtheaddedvalueofanIGRAinresponsetoamycobacterial
UniversityofKualaLumpur,Malaysiaantigenassociatedwithlatency,theheparin-bindinghaemagglutinin(HBHA).Allbutone
,
+
HomertonUniversityHospitalNHSTSTpatienthadapositiveHBHA-IGRA,
FoundationTrust,UnitedKingdomHBHA-IGRAwasalsopositivefor12/35TST-QFT-
*Correspondence:patients(12withHBHA-IGRA+)of8chemokinesinadditiontoIFN-grevealedabroadarray
¸
FrancoiseMascart+---
francoise.******@-inducedchemokinesforTSTQFTandTSTQFTpatients,comparedtoamore
restrictedpatternforTST+QFT+
Specialtysection:
Thisarticlewassubmittedto
MicrobialImmunology,
asectionofthejournalapproachmayhelpinprioritizingpatientswhoshouldreceiveprophylacticanti-TB
FrontiersinImmunologytreatmentbeforestartingbiotherapiesinordertoreducetheirnumber.
Received:26February2021
Accepted:17May2021Keywords:psoriasis,Tumornecrosisfactor-ainhibitors,latenttuberculosisinfection,tuberculinskintests,
Published:03June2021interferon-g-releaseassays,QuantiFERON,heparin-bindinghaemagglutinin
Citation:
BenhadouF,DirixV,DomontF,
WillaertF,VanPraetA,LochtC,INTRODUCTION
MascartFandCorbièreV(2021)
TuberculosisRiskStratification
Psoriasisisafrequentskininflammatoryconditionwithaworldwideprevalenceof3%,
ofPsoriaticPatientsBefore
Anti-TNF-(1,2).
:,suchaspsoriaticarthritisandcardiovasculardiseases,
doi:.672894leadingtotheconceptofasystemicimmune-mediatedinflammatorydisease(IMID)(3).Significant
FrontiersinImmunology||Volume12|Article672894
progresshasbeenmadeinthemanagementofpsoriasisbythesensitivityinpatientsalreadyreceivingimmunosuppressivedrugs
useoftargetedbiologicaldrugs,initiallylimitedtotumor().
necrosisfactor-a(TNF-a)inhibitors(4).PatientsreceivingUsingeitherTSTorIGRAtodetectLTBIbeforetheinitiation
TNF-a-targetedtherapieshaveanincreasedriskofofTNF-a-targetedagentsishowevernotoptimalasprophylactic
reactivationofalatentMycobacteriumtuberculosisinfectionanti-TBtreatmentintheseselectedpatientsdidnotprovidethem
(LTBI),andalthoughtherearefewanddiscrepantspecificcompleteprotectionfromdevelopingaTB(15).Therefore,in
reportsinpsoriaticpatients(5),theriskofactivetuberculosisadditiontoacarefulevaluationofthepatient’sriskfactorsfor
(aTB)is,accordingtoarecentmeta-analysis,doubledforLTBIandchestX-rayradiographytoexcludeaTB,adualstrategy
patientstreatedwithanti-TNF-a(6).Theuseofbiologicalperformingbothtests(TSTandIGRA)isnowlargely
drugstotreatpsoriasiswasfurtherextendedtootherrecommendedtoreduceanypossibleriskofdevelopingaTB.
therapeuticagentstargetingtheinterleukin(IL)-23/IL-17axisThepositivityofanyofthesetestsforthediagnosisofLTBI
(7,8),buttheirpotentialriskofreactivationofLTBIisnotyetshouldbeconsidered(16).Unfortunately,neithertheTST,nor
firmlyestablished(9).theIGRAallowedustodetectpatientswiththehighestriskof
Classically,
presenteitherasaTBorasLTBIdefinedbythepresenceofdifferentstageswithinthespectrumofLTBIandarepositive
immunologicalresponsestomycobacterialantigensinabsenceofbothinLTBIsubjectsandinpatientswithaTB(17).
clinicalsymptomsofdisease(10,11).LTBIsubjectsarethoughtGiventhelimitationsoftheTSTandthecommercialIGRAs
topresentalife-longriskofreactivationoftheinfection,with5todiagnoseLTBIinpatientswithIMID,andtheirinabilityto
to15%ofthemdevelopingaTBduringtheirlifetime(11).RecentselectamongLTBIsubjectsthosewhohavethehighestriskto
datahoweverchallengedthisconceptandindicatedthatLTBIreactivatetheinfection,weevaluatedinthisstudytheadded
comprisesarangeofinfectionoutcomesassociatedwithdifferentvalueofanIGRAbasedonthelatency-associatedantigen
bacterialpersistenceandhostcontainment,fromclearedheparin-bindinghaemagglutinin(HBHA),reportedtodetect
infectiontolow-gradeTB(10).ItbecameevidentthattheseLTBIwithhighsensitivityandspecificity(18),andwe
lastindividualsareprobablymoreatrisktoreactivatethecomparedtheresultsoftheHBHA-IGRAtothoseoftheTST
.
Inviewofthehigherriskofpsoriaticpatientstoreactivate
LTBIwhenreceivingTNF-a-targetedtherapies,detectionofLTBI
beforeinitiatingbiotherapiesismandatoryandessentialtoMATERIALANDMETHODS
providepreventiveanti-TBtreatment(9,12).Thisdetectionis
nowadaysbasedontheclassicaldefinitionofLTBI,
detectionofmemoryTcellresponsestomycobacterialantigens,Forty-nineadultpatientssufferingfrompsoriasiswere
revealingthepresenceofhostsensitizationtotheseantigens(11).prospectivelyrecruitedfromtheoutpatientclinicofthe
Thetuberculinskintest(TST)isthegoldstandardforthisDermatologydepartmentatthe“hôpitalErasme”aspartof
detectionsincedecades,inspiteofpossiblefalse-positiveresultstheirevaluationbeforestartingbiotherapy(EthicsCommittee
inBacillusCalmette-Guérin(BCG)-vaccinatedsubjectsandin021/406,P2012/082).TBscreeningperformedforallparticipants
non-tuberculousmycobacteria(NTM)-infectedpatients(13),andincludedTST(,SSI,
despitepossiblelowersensitivityinpatientssufferingfromIMIDCopenhagen,DK),chestX-ray,
withimmune-suppressivetreatmenthistory(14).Therefore,TST72hoursandtheresultswereassessedinthecontextofthe
hasbeenreplacedinseveralcountriesbyinterferon-gamma(IFN-patient’
g)releaseassays(IGRAs).ThesebloodtestsmeasuretheIFN-gfactors,TST-QFT-patientswithoutchestX-Raysignsuggesting
secretionwithinwholebloodorbyperipheralbloodmononuclearaTB,wereconsideredasnon-+
cells(PBMC),uponinvitrostimulationwithpeptidesfromtheand/orTST+patients(indurationsize≥15mm)wereconsidered
mycobacterialantigensearly-secretedantigenictarget-6(ESAT-6),
culturefiltrateprotein-10(CFP-10),(9).toreactivateLTBI,patientswithaTSTpositivitybetween10and
TheseIGRAs,commerciallyavailableastheQuantiFERON(QFT)14mmwerealsoconsideredasbeingLTBI().Four
(Qiagen,Hilden,Germany)ortheT-(Oxfordpatientsweretreatedwithmethotrexateatthetimeofinclusion.
Immunotec,Oxford,UnitedKingdom),-TNF-aantibodiesandwere
tuberculosisinfectionthanTST,
,theywereinitiallyevaluatedforpossibleLTBIbeforetheirfirst
theybothincludepositiveandnegativecontrolstoidentifyanti-TNF-atreatment,3/10wereconsideredLTBIandreceived
,theywerereportedbyseveralatthattimeprophylacticanti-TBtreatment.
authorstohavelowersensitivitythaninitiallythoughttodetect
(14),sothatinQuantiFERON-TBGold
Belgium,alowTBincidencecountry(<10newcases/(QuantiFERON-TBGoldIn-tube)wasperformed
inhabitants/year)withalowBCGvaccinationcoverage,IGRAsareaccordingtothemanufacturerinstructions().
recommendedonlyincaseofdoubtfulTSTresults,ortoincreaseApositiveQFTtestwasdefinedas≥-greleased
FrontiersinImmunology||Volume12|Article672894
inresponsetothemycobacterialpeptides,aftersubtractionofthesubtractedfromthoseobtainedwithantigenstimulation.
concentrationobtainedfortheunstimulatedcondition,withaConcentrationsbelowthedetectionlimitwereallocatedan
result>25%,whilstresultsexceedingtheassay’s
upperlimitofdetectionwereattributedtheconcentration
HBHA-IFN-gReleaseAssay(IGRA),thepositivitylimit
PBMCwereisolatedfromfreshbloodsamplesandinvitrowasarbitrarilydeterminedasbeingminimum4timesthedetection
limitormaximum2timesthemedianconcentrationobtainedfor
stimulatedduring24hoursat37°Cunder5%CO2with2µg/
mlHBHA,leftunstimulatedinculturemedium(negativenon-infectedpatientswhencytokines/chemokineswere
fi
control)µg/±20%of
enterotoxinB(SEB,Sigma-Aldrich,Bornem,Belgium)thecut-
(positivecontrol).IL-7wasaddedintheculturemediumat1representingtheintensityofcytokine/chemokineconcentrations
ng/mltoincreasethesensitivityofthe24hrsassay(19).HBHAwasestablishedforeachanalytefromnegativevaluestodoubtful,
waspurifiedfromMycobacteriumbovisBCGculturelowandstrongcytokine/chemokineconcentrations.
supernatantsbyheparin-Sepharosechromatography
(SepharoseCL-6B;PharmaciaLKB,Piscataway,NJ)(20).TheStatisticalAnalysis
boundmaterialwaselutedbya0-500mMNaClgradientandDifferencesbetweenseveralgroupswereassessedbythenon-
wasfurtherpassedthroughareverse-phasehigh-pressureliquidparametricKruskal-Wallistest,followedbythenon-parametric
chromatography(HPLC;BeckmanGoldSystem),-inducedIFN-g
NucleosilC18column(TSKgelSuperODS;Interchim)concentrationsattwodifferenttime-pointswereevaluatedby
%<(*)wasconsidered
fi
performedbyalinear0-80%
elutedat60%acetonitrile(21)..
revealedasinglepeakandanalysisbySDS-PAGEshoweda
singlebandafterCoomassie-bluestaining,indicatingtheabsence
Cellculturesupernatantswerefrozenat-20°Cuntil
measurementofsecretedcytokines/-
concentrationsweremeasuredbyELISA(19).IFN-gInfectioninPsoriaticPatientsAccording
concentrations<50pg/mlinthenon-stimulatedconditiontoStandardCriteria
and>200pg/mlinthepositivecontrolswererequiredforInBelgium,alow-TBincidencecountry,forty-nineadultpatients
,IFN-gsufferingfrompsoriasiswereprospectivelyrecruitedfromthe
concentrationsobtainedundernon-stimulatedconditionswereoutpatientclinicoftheDermatologydepartment(hôpital
subtractedfromthoseobtainedinresponset