Publication:
Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis

dc.contributor.coauthorEngel, Bastian
dc.contributor.coauthorDiestelhorst, Jana
dc.contributor.coauthorHupa-Breier, Katharina Luise
dc.contributor.coauthorKirchner, Theresa
dc.contributor.coauthorHenjes, Nicole
dc.contributor.coauthorLoges, Stephanie
dc.contributor.coauthorJanczyk, Wojciech
dc.contributor.coauthorLalanne, Claudine
dc.contributor.coauthorZachou, Kalliopi
dc.contributor.coauthorOo, Ye H.
dc.contributor.coauthorGournay, Jerome
dc.contributor.coauthorPape, Simon
dc.contributor.coauthorDrenth, Joost P. H.
dc.contributor.coauthorRenand, Amedee
dc.contributor.coauthorDalekos, George N.
dc.contributor.coauthorMuratori, Luigi
dc.contributor.coauthorSocha, Piotr
dc.contributor.coauthorMa, Yun
dc.contributor.coauthorBaumann, Ulrich
dc.contributor.coauthorManns, Michael P.
dc.contributor.coauthorWedemeyer, Heiner
dc.contributor.coauthorJunge, Norman
dc.contributor.coauthorJaeckel, Elmar
dc.contributor.coauthorTaubert, Richard
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorArıkan, Çiğdem
dc.contributor.kuauthorYüksel, Muhammed
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-12-29T09:37:38Z
dc.date.issued2024
dc.description.abstractObjectiveThe detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH.DesignpIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285).ResultsIgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31-73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6-20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21-34% higher accuracy than conventional autoantibodies, was positive in 43-75% of children with AIH and normal IgG and independent from treatment response.ConclusionDetecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue4
dc.description.openaccessGreen Published, hybrid
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipWe thank Szilvia Ziegert, Beate Junk and Konstantinos Iordanidis from the "immune tolerance working group" at Hannover Medical School for technical assistance in performing the experiments. We thank Emily A Bosselmann for proofreading of the final manuscript.
dc.description.volume18
dc.identifier.doi10.1007/s12072-024-10695-1
dc.identifier.eissn1936-0541
dc.identifier.issn1936-0533
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85197707276
dc.identifier.urihttps://doi.org/10.1007/s12072-024-10695-1
dc.identifier.urihttps://hdl.handle.net/20.500.14288/22435
dc.identifier.wos1265420100002
dc.keywordsAntinuclear antibody
dc.keywordsAnti-smooth muscle antibody
dc.keywordsAnti-liver kidney microsomal antibody
dc.keywordsAnti-soluble liver antigen/liver pancreas
dc.keywordsHuntingtin-interacting protein 1-related protein (HIP1R)
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofHepatology International
dc.subjectGastroenterology and hepatology
dc.titleDetection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorYüksel, Muhammed
local.contributor.kuauthorArıkan, Çiğdem
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
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relation.isOrgUnitOfPublicationd02929e1-2a70-44f0-ae17-7819f587bedd
relation.isOrgUnitOfPublication.latestForDiscovery91bbe15d-017f-446b-b102-ce755523d939
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