biostudies-literatureZecher BFCCR NIH HHSBundesministerium für Bildung und ForschungFrederick National Laboratory for Cancer ResearchDeutsche ForschungsgemeinschaftEuropean Research CouncilLandesforschungsförderung HamburgNCI NIH HHSDaisy Hüet Roel FoundationAcademy of Medical Sciences325-337https://www.ebi.ac.uk/biostudies/studies/S-EPMC10850656biostudies-literatureUnknown73(2)<h4>Objective</h4>Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.<h4>Design</h4>Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activatGut&lt;i&gt;HLA-DPA1*02:01~B1*01:01&lt;/i&gt; is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells.PMC10850656N/AHHSN261200800001EHHSN261200800001CCRU306 Primary sclerosing cholangitisEXC 2167-390884018EL 831/7-1 (project number 507145175)LFF-FV78SFB841/SP2grant agreement n° 88483001KI2110884830SGL020\1037Farkkila MLazaridis KNFruh THaussinger DGores GHoelzemer AInternational PSC Study Group (IPSCSG)Huynh DSchrumpf EMartin MPSchreiber SGeier AAnderson CAYtting HMilkiewicz PHirschfield GMRorsman FMuller LMdeValleVillalba MBShapiro DKnuth ACorpechot CLohse ATrauner MAltfeld MSauer PKarlsen THWeersma RKMarzioni MPoch TManns MELleo APonsioen CYZweers SFabris LFloreani AFolseraas TBurroughs AMarschall HULevy CFranke AKeitel VJones DLindor KHarley HBowlus CLSchaap FGLiu JZCleynen IAdams DHInvernizzi PFickert PVermeire SKretschmer PVesterhaug MPlentz RBaumdick MENiersch JSandford RNJuran BDBlack DSebode MLankisch TMulcahy HELiaskou EBjorkstrom NPoupon RSchumacher UKremer AETaylor-Robinson SDMammari SAEksteen BBoberg KMBrias SStrazzabosco MRazumilava NZecher BFBurt AGotthardt DMullhaupt BSchirmacher PWehmeyer MHZimmer VPereira SEverson GAabakken LHabermann RWeismuller TOldhafer KJChazouilleres OHabior AWebster GUeno YChapman RWGoldberg DOhira HBeuers UMerwe SVCarrington MTanaka AStraub BKKhan SAMason ANiehrs AMelum EHov JSchramm CKaser AAlexander GJPares AKarpen SJKorner CSteenbergen WVHelmke SCulver ELYuki YAlmer SSauter GSelmi CDegenhardt FWilliamson KGlow DFehse BTalwalkar JPadoan BMertens JCBjornsson EHalilbasic EMells GFBergquist AEllinghaus EEllinghaus DDanekas Jvan Buuren HRSchroder-Schwarz JShibolet OJansen PLLindstrom LFevery JSchloer SWunsch EBunders MJHousset CRushbrook SMfalse&lt;i&gt;HLA-DPA1*02:01~B1*01:01&lt;/i&gt; is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells.<h4>Objective</h4>Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.<h4>Design</h4>Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activat2024-01-01T00:00:00Z2024 Jan2026-06-12T05:48:16.156Z2026-06-12T03:08:22.092ZS-EPMC108506563778889510.1136/gutjnl-2023-329524