1. MolecularandFunctional Immune AssaysasNon-Invasive DiagnosticToolstoAssessthe Riskof Acute
Subclinical RejectionAfterKidneyTransplantation
O. Bestard,1,2
E.Crespo,1
T. Sigdel,2
S.Roedder,2
Y.Ng,2
J.Cruzado,1
M. Lúcia,1
S.-C.Hsieh,1
T.Tran,1
J.
Grinyó,1
M. Sarwal.1
1
KidneyTransplant Unit, Bellvitge UniversityHospital, Barcelona, CAT, Spain
2
Department ofTransplant Surgery, UCSF, SanFrancisco, CA.
Subclinical allograftrejection(sc-AR) isstillamaincause of allograftlossthatcan onlybe assessed
throughinvasive surveillancebiopsies.We soughttoinvestigatewhetherthe combinationof novelnon-
invasive biomarkersatthe molecularandimmune functionallevel couldhelpidentifyingpatientsatrisk
of sc-ARafterkidneytransplantation.
Methods:
We combinedthe assessmentof the donor-specificIFN-γ T-cellELISPOTwithahighlysensitiveand
specifictranscriptional biomarkertestinperipheral bloodsamplespredictingkidneysolidorganclinical
rejection(KSORT) usingqPCR,inagroup of 75 consecutive kidneytransplantpatientsatthe time of 6-
monthprotocol biopsies.
Results:
All patientsreceivedCNI-basedIMSandeitherrATG or basilimab.22/75(29%) patientsshowed
histological lesionsof sc-AR(18TCMR, 5 ABMR and 1 mix TCMR/ABMR), 22 showedborderline (BL)
lesionsand31 a stable (STA) parenchyma.The KSORTshowedahigh-risk(HR) andlow-risk(LR) scoresin
23% and77% patients,respectively.The T-cell ELISPOTwaspositivein41% of patients,whereas
negative in59%.82% and 70% patientswithBL lesionsshowedaLR KSORTand negative T-cell Elispot,
respectively.The KSORTcorrectlyclassifiedasLR 98%) STA andas HR 70% sc-AR (p<0.001), further
discriminatingasHR all (100%) sc-ABMR and 62.5% sc-TCMR (p<0.001). The d-sT-cell ELISPOTaccurately
ruledoutthe presence of sc-TCMR in72% and predicteditspresencein83.3% (p<0,001), whereasitdid
not discriminate patientswithsc-ABMR(p=NS).transplantrecipientswithapositive T-cellELISPOT
showedsignificantlyhighertubulitisandinterstitiuminfiltratesthanpatientswithnegativeaELISPOT
test,whereasthose patientswithapositive KSORTdidshow bothhighertubulitis(at) andinterstium
infiltrates(ai) aswell ashigherglomerulitis(ag) andperitubularcapillarities(ptc).
Conclusions:
Combininganon-invasivemolecularandfunctional cellularimmuneassayallowsanaccurate
identificationof patientsdevelopingsc-AR,dissectingthe mainalloimmune effectormechanism
responsible of it.