High-Density Modified Histone Peptide Arrays for Tracking Patient Response

PROJECT SUMMARYThe goal of this project is to develop an epigenetic microarray platformEpiSeraTMas a diagnostic and staging tool for autoimmune diseasesAutoantibodies directed against nuclear antigensincluding histone proteins and double stranded DNAdsDNAare prevalent in serum of patients with systemic lupus erythematosusSLErheumatoid arthritisRAand other autoimmune diseasesAssays to detect circulating autoantibodies toward histones and or dsDNA are commonly used to help diagnose and stage SLEand assays capturing autoantibodies with citrullinated histone peptide antigens are highly predictive and selective for the diagnosis of RAHoweverthese tests fail to detect disease in all patients and poorly reflect the heterogeneous nature of these complex pathologiesThe development of new autoimmune biomarkers are desperately needed and will enable improved personalized treatment strategies as well as provide clinicians with indicators to better track disease progression and therapy responseNucleosomes are heavily decorated with histone post translational modificationsPTMsand DNA methylationWe hypothesize that capturing plasma autoantibodies with histone and DNA antigens harboring defined modifications has clinical potential for autoimmune disease diagnosisstagingand treatment responsePreliminary data suggests that serum from SLE patients contains autoantibodies specific for unique sets of histone PTMsThe innovation of this project is the development of a microarray platform to profile a patientsautoantibody epigenetic footprintcomprised of both DNA and histone modificationsas a next generation diagnostic assayFor proof of conceptwe will focus on patients with SLE and RAthese pathologies are strongly associated with high levels of nuclear targeting autoantibodiesHerewe will develop EpiSeraa new specialized microarray platform that includes andgtunique modified peptides and DNA oligos covering major nucleosome modifications for the rapid capture and characterization of human immunoglobulinIgisotypesAimEpiSera will containsubarraysenabling users to probe multiple patient samplesdilutions per arrayWe will use EpiSera to profile autoantibodies from patients with SLE and RAAimThis project will be considered successfully complete when EpiSera can be used to distinguish SLE and RA patients from each other and from healthy controlsOur study has the potential to develop a robust clinical tool to identify new biomarkers for SLERA diagnosisstagingand therapeutic responseIn Phase IIwe will expand the scope of our preclinical studies to better define key epigenetic profiles that delineate SLE and RA patients based on disease severityprogressionetcAt the conclusion of Phase IIwe will begin to market EpiSera for pre clinical and research applications and be well positioned to initiate and receive FDAkclearance PROJECT NARRATIVEAutoantibodies directed against nuclear antigensi ehistone proteins and or DNAare prevalent in blood from patients with autoimmune diseaseDiagnostic assays used to detect these autoantibodies are currently limitedas they fail to identify disease in all patients and poorly reflect the heterogeneous nature of these complex pathologiesHereEpiCypher is developing an epigenetic microarray platformEpiSeraTMfor the detection of circulating nuclear autoantibodies that target histone and DNA modifications as next generation biomarker panels for autoimmune diseasesThis innovative platform will enable the identification of new epigenetic biomarkers for autoimmune disease diagnosisstagingand therapeutic response