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Cerebral Vein Thrombosis in the Antiphospholipid Syndrome

13 dic 2021 and Other Autoimmune Disorders Service de Médecine Interne 2

onset ofsymptoms. ThusiTreg havesignificant positiveeffects onPIL, whichmay have consequencesforfuture approaches intreatin gSLE.

Disclosureof Interest:None declared

DOI:10.1136/annrheumdis-2018-eular.6090

FRI0260POLYMORPHISMSOFSTAT 4AND MIR146APREDICT

THE ACHIEVEMENTOF5 YEARSREMIS SIONIN

PATIENTSWITH SYSTEMIC LUPUSERYTHEMATO SUS

C. Perricone

1 ,C.Ciccacci 2 ,F.Ceccarelli 1 , G.Me ttola 1 , I.Lec cese 1 , F.R.Spine lli 1

C. Alessandri

1 , C.P oliti 2 , A.Lat ini 2 ,G.Novelli 2 , G.V alesini 1 , P.Bor giani 2

F. Conti

1 1 LupusClin ic,Rheumatolog y,DepartmentofInternalMedi cine,Sapienza

UniversityofRome;

2

DepartmentofBiomedi cine andPrevention,Section of

Genetics,Universityo fRome"TorV ergata", Rome,Italy Background:Systemiclupus erythematosus(SLE) isa chronic autoimmune dis- ease witha complexpathogenesis inwhich genesand environmental factors interact leadingto aprotean clinicalpicture. Treat-to-target recommendations have identified'remission'as atarget inSLE, sinceachiev ementof remission improves theoutcom eandisassociated withdecre aseddamage progression. Nonetheless,predic tingfactorsforthe achievementof remission arelacking. Itis likely thatgenes associatedwith SLEpathogenesis mayinfluence thedisease course. Objectives:Thus, ouraim wasto analysepreviously identifiedloci associated with SLEina cohortof SLEpatie ntsto evaluatetheir influenceon remission achievement. Methods:We recruited117Italian SLEp atients.A panelof 34SNPsin19 genes involved inimmune response,autopha gyand inflammation,wasselected.SNPs genotypingwas performed byallelicdiscrimination assayby TaqManassays (Applied Biosystems,Foster City,CA,USA)and ABIPRISM 7000.The mainclini- cal/laboratoryfeature s(includinginjuryindex anddisease activity)were collected on anelectronic platform.Remis sionwas definedaccordingtoZen etal. 1 and evaluated over5 years.A genotype/phenotype correlation analysiswas performed. Results:The variantalleles ofrs7574965 (STAT4)(p<0.001) andrs291 0164 (MIR146a) (p=0.031)were significantly associatedwithlackof achievement of5 years remissionin SLE.Specific ally,patie ntscarryingtheC alleleofMIR146a were lesslikely toachiev e5 yearsremission(p=0.01,OR 0.235,9 5%CI 0.074-

0.752)as wellas toachieve remissionafter 1,2 and3 yearsof evaluation

(p=0.002, p=0.001,p=0.002,respectively). Amongthe clinicaland laboratoryfea- tures, 5years remissionwas lesslikely tobe achievedby patients whohad arthri- tis intheir clinicalhistory (p=0.007),and whotested positive foranti-dsDNA (p=0.005). Ina multinomial logisticregressionanalysis,arthrit is(p=0.022, Exp(B) =0.255, 95%CI 0.079-0.820), anti-dsDNA(p=0.003, Exp(B)=0.166,95% CI

0.051-0.537) andMIR 146ars2910164gen evariant(p=0.046, Exp(B)=0.250,

95% CI0.064 -0.974)were confirmedto beindependent riskfacto rsfor

unreached5 yearsremiss ion(ta ble1).

Abstract FRI0260-Table 1

REMISSION Exp

(B)Exp (B)95% CI

Lower Upper

Arthritis0255 00790,82

anti- dsDNA0166 00510537

STAT40354 0,111139

mir146A0,25 00640974 Conclusions:We describefor thefirst timethe contributionof STAT4and MIR146aSNPs aspredicting factors forthe achievementof5years remissionin SLE. Nogenetic studyhas beenperformed sofar inSLE, whilea geneticprof ileof patientsmay beuseful topredict thedisease outcome.

REFERENCE:

[1] Zen,et al.Ann RheumDis. 2017Mar;76(3):562 -565.

Disclosureof Interest:None declared

DOI:10.1136/annrheumdis-2018-eular.6936

FRI0261ASSESSMENTOF AUTOPHAGE FUNCTIONIN

SYSTEMICLUPUS ERYTHEMATOS USINRESPECTOF

HYPERLIPIDEMIAANDIMMU NOSUPPRESS IVEDRUGS

A.S.Ham ada

1 , M.I.aref 1 , W.A.salah din 2 1

ClinicalImmuno logy,AlAzhar

UniversityHospital, Cairo;

2

Rheumatology,BenhaUniver sityHospi tal,Benha,

Egypt Background:Autophagy isan orchestratedhomeostatic process toelim inate unwanted proteinsand damaged organelles.Lipidtur nover,aswell,is controlled by autophagythrough aprocess describedas lipophagy.Defective lipophagyhas been alreadylinked toimpo rtantmetabolic disorderssuchasfatty liver,obesity and atherosclerosis. Objectives:Assessmentof autophagyfocusing onlipids regulationin untreated newly diagnosedsystem iclupusErythematosus (SLE)patie ntsandafterthree months oftreatment withimmunosuppre ssivedrugs . Methods:Subjectsin thisstudy havebeen dividedinto threegroups. Group1 included60 newlydiagnosed SLEpatie ntsbefore receiving anytreatment,group2 includedthe samesubjects ofgroup 1after threemonths oftre atmentwith immu- nosuppressivedrugs andgroup 3include d30 healthydonors ofmatchedageand sex asa controlgroup. Foreach subject,diseas eactivity wasassessed by(SLE- DAI) score,lipid profilewas measuredin addition toevaluation oflipids uptake, enhancedphagocyt osisandintracellular killingabilit yofmonocytesand neutro- phils usingSudan BlackB stainand Nitrobluetetrazolium stainmixed withlatex particles coatedwith antibodies.Micros copicpictures werecapturedandquanti- fied byImageJ. Results:95% ofpatients werefemales (57/60)with meanofage(39.7±8.6).Mean of SLEDAIscore ingroup 1was (18.6±3.4)decre asedin group2 (3months after treatment)to (10.4±4.2).There wasa positive correlationbetween totalcholes- terol, LDLand triglyceridesand diseaseactivity(SLED AIscore) (r=0.677, r=0.603 andr=0.718; respectively).On thecontrar y,There wasa negativecorre- lationbetween HDLand diseaseactivity(r= ?0.396).Furthermo re,therewasa negativecorrelat ionbetweenlipidcontent ofcells andintracellu larkilling anddis- ease activity(r=?0.258 andr= ?0.324;respe ctively).After3months, 100%of patientswere takingCorticosteroi dsand Hydroxychloroquine(60/60).18.3%of patientsreceived Azathioprine(11/60), 40.0%receivedCyclopho sphamide(24/

60) and15% receivedMycoph enolate(9/60)besides CorticosteroidsandHydrox-

ychloroquine.Comparin ggroup2to group1, therewas significant increasein cholesterol,L DLandtrigycerides (p=0.027,p=0.021 andp=0.017;respectively) while HDLshowed insignificantdiffere nce(p=0.0740).Lipid contentincellsand intracellularkilling significantly decreased(p=0.0322andp=0.0271; respectively). Conclusions:Autophagyis deficientin patientswith SLEaggravated byimmu- nosuppressivedrugs sothey aremor esusceptible toinfections anddyslipidemia. Consequently,lipid loweringdrugs aredefin itelyrequired todecrease comorbidity.

Disclosureof Interest:None declared

DOI:10.1136/annrheumdis-2018-eular.4609

FRI0262MONITORINGDISEA SEACTIVITYIN SYSTEMICLUPUS

ERYTHEMATOSUSWITHDIGIT ALELISA

QUANTIFICATIONOFSERUM INTERFER ON-A

S. Mouries-Martin

1 ,A.Ma thian 1 ,K.Dorgham 2 ,H.Devilliers 3 , F.Coh en-Aubart 1 ,L.

N. GarridoCastill o

2 , J.Har oche 1 ,M.Hie 1 , M.P inetonDeChambrun 1 , M.M iyara 1

M. Pha

1 ,D.LêThiHuong 1 ,F.Rozenberg 4 , G.Go rochov 5 , Z.Amo ura 1 1

French

NationalRefer ralCenterforSyst emicLupusEryth ematosus ,Antiphospholi pid AntibodySyndrom eandOtherAutoimm uneDis orders,Ser vicedeMédecine Interne2,Inst itut E3M,Assistance Publique-HôpitauxdePar is(A PHP),

GroupementHospital ierPitié-Salpêtrière;

2

InsermUMRS 1135,Centre

d'ImmunologieetdesMala dies Infecti euses(CIMI-Par is),SorbonneUniversités,

UPMCUn ivParis 06,Paris;

3 CentreHosp italierUniversitairede Dijon,Hôpital François-Mitterrand,ServicedeMédecine Interne2etCent red 'Investigation

Clinique,InsermCI C1432,DIJ ON;

4

ServicedeVir olog ie,AssistancePublique -

HôpitauxdePar is(A PHP),Hôpit alCochin;

5

InsermUMRS1 135,Centre

d'ImmunologieetdesMala dies Infecti euses(CIMI-Par is),AssistancePublique- HôpitauxdePar is(A PHP),Groupe mentHospitalier Pitié-Salpêtrière,Paris,Fr ance Background:To date,anti-dsD NA-Ab titration,better achievedwith theFarr test, hasbeen usedto monitorglobal disease activityin systemiclupus erythema- tosus (SLE).Indeed, anti-DNA-Ab-positivityis associatedwith overall SLEactiv- ity. However,the sensitivity andspecificityof thatassociation arerelativelylow. The closeassociationbetween Interferonalpha (IFNa) expressionand SLEactiv- ity suggeststhat monitoring thiscytokinemight helpphys iciansbetterevaluate

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