Tissuebiopsyoftransplantedorgansremainsthegoldstandardforevaluationofrejectionorotherpathologiccausesofallograftdysfunction.Inrecentyears,organtransplantpathologyhasevolvedwithrecognitionofantibody-mediatedrejection(ABMR)inkidneyandalmostalltransplantedsolidorgansystems.Immunohistochemical(IHC)analysisofC4dhasamajorroleindiagnosisofABMR.InABMR,antibodybindingtoendothelialsurfacesoftenactivatestheclassiccomplementpathwayviaC1q.C1qactivatesC4,whichis,inturncleavedandactivatesC3,C5andthemembraneattackcomplex(1-4).Thisprocessdamagesendothelium,causescapillaritisandresultsintherecruitmentofinflammatorycellstositesofcomplementactivation(1-4).Althoughtheincitingantibodiesandothercomplementsplitproductsaredegradedorcarriedawayintheserum,theC4dfragmentremainscovalentlyboundtosurfaces(viaathioesterbond).RecentstudieshavefocusedonIHCscoringandinterpretationofC4dstainingtoevaluateABMRandcorrelatingitwithhistologicfindings,thisoftenmanifestsasintracapillaryinflammatorycells,termedcapillaritisandimmunostainingofC4ddepositionincapillariesasahallmarkofantibody-mediateddamage.However,activationofthecomplementviathemannosebindinglectinpathwayalsoproducesC4d;therefore,C4dstainingisneitherentirelyspecificnorperfectlysensitive(2-4).ERG,anETS-familytranscriptionfactorisconstitutivelyexpressedinendothelialcells.Itregulatesendothelialcelldifferentiation,angiogenesisandexpressionofseveralendothelial-specificantigensandisalsorequiredforembryonicstemcellstodifferentiateintoendothelialcells(5).Thus,thecombinationofC4dandERGwithamultiplexedmembranous(C4d)andnuclear(ERG)stainingpatternwouldfacilitatetheidentificationofthediseasedendothelialcellsandsupportadiagnosisofABMR.
| ByLetter | E |
|---|---|
| Antigen | N-terminalERG,InternalsequenceofhumanC4 |
| Clone | 9FY,A24-T |
| Format | Predilute |
| IntendedUse | IVD |
| Isotype | IgG1,IgG |
| Localization | Nuclear,Basementmembrane/Cytoplasm |
| PositiveControl | Renalallografttissue |
| Volume | 6.0ml |
References:
1.FeuchtHE.ComplementC4dingraftcapillaries—themissinglinkintherecognitionofhumoralalloreactivity.AmJTransplant.2003;3:646–52.
2.CohenD,etal.ProsandconsforC4dasabioMarker.KidneyInt.2012;81:628–39.
3.NickeleitV,MihatschMJ.Kidneytransplants,antibodiesandrejection:isC4damagicmarker?NephrolDialTransplant.2003;18:2232–39.
4.BohmigG,RegeleH.Diagnosisandtreatmentofantibody-mediatedkidneyallograftrejection.TransplInt.2003;16:773–87.
5.MiettinenM,etal.ERGexpressioninepithelioidsarcoma:adiagnosticpitfall.AmJSurgPathol2013;37:1580–5.
6.CenterforDiseaseControlManual.Guide:SafetyManagement,NO.CDC-22,Atlanta,GA.April30,1976“DecontaminationofLaboratorySinkDrainstoRemoveAzideSalts.”
7.ClinicalandLaboratoryStandardsInstitute(CLSI).ProtectionofLaboratoryWorkersfromOccupationallyAcquiredInfections;ApprovedGuideline-FourthEditionCLSIdocumentM29-A4Wayne,PA2014.
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