title: Identification of Pathway-Specific Serum Biomarkers of Response to Glucocorticoid and Infliximab Treatment in Children with Inflammatory Bowel Disease.
abstract: OBJECTIVE
  Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.
  
  
  METHODS
  We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed by quantitative real time PCR. Concordance of longitudinal changes between the groups was used to identify markers responsive to treatment. Bioinformatic analysis was used to build insight into mechanisms of changes in response to treatment.
  
  
  RESULTS
  We identified 18 proteins and three miRNAs responsive to both prednisone and infliximab. Eight markers that decreased are associated with inflammation and have gene promoters regulated by nuclear factor (NF)-κB. Several that increased are associated with resolving inflammation and tissue damage. We also identified six markers that appear to be steroid-specific, three of which have glucocorticoid receptor binding elements in their promoter region.
  
  
  CONCLUSIONS
  Serum markers regulated by the inflammatory transcription factor NF-κB are potential candidates for pharmacodynamic biomarkers that, if correlated with later outcomes like endoscopic or histologic healing, could be used to monitor treatment, optimize dosing, and enhance drug development. The pharmacodynamic biomarkers identified here hold potential to improve both clinical care and drug development. Further studies are warranted to investigate these markers as early predictors of response, or possibly surrogate outcomes.
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Heier
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Fiorillo
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's National Health System, Washington, DC, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Chaisson
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.|ReveraGen BioPharma, Rockville, MD, USA.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Damsker
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.|ReveraGen BioPharma, Rockville, MD, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, District of Columbia, USA.|Division of Gastroenterology, Hepatology, and Nutrition, Children's National Health System, Washington, DC, USA.
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Conklin