title: Investigating CD11c expression as a potential genomic biomarker of response to TNF inhibitor biologics in whole blood rheumatoid arthritis samples.
abstract: BACKGROUND
  Gene expression profiling is rapidly becoming a useful and informative tool in a much needed area of research. Identifying patients as to whether they will respond or not to a given treatment before prescription is not only essential to optimise treatment outcome but also to lessen the economic burden that such drugs can have on healthcare resources. In rheumatoid arthritis (RA), there is of yet no genetic/genomic biomarker which can accurately predict response to TNF inhibitor biologics prior to treatment, despite much interest in this area. Multiple studies have reported findings on potential candidate genes; however, due to relatively small sample sizes or lack of sufficient validation, results have been disappointingly inconsistent. The aim of this research was to further explore the predictive value of a previously reported association between CD11c expression and response to the TNF inhibitor biologics, adalimumab and etanercept.
  
  
  METHODS
  Real-time qPCR was performed using whole blood RNA samples obtained from seventy-five rheumatoid arthritis patients about to commence treatment with a TNF inhibitor biologic drug, whose response status was determined at 3-month follow-up using the EULAR classification criteria. Relative quantification of CD11c using the comparative CT method outputted differential expression between good-responders and non-responders as a fold-change.
  
  
  RESULTS
  Relative expression of CD11c in patients receiving TNF inhibitor biologics yielded a decrease of 1.025 fold in good-responders as compared to non-responders (p-value = 0.36). Upon stratification of patients dependent upon the specific drug administered, adalimumab or etanercept, similar findings to the full cohort were observed, decreases of 1.015 (p-value = 0.33) and 1.032 fold (p-value = 0.13) in good-responders compared to non-responders, respectively.
  
  
  CONCLUSIONS
  The results from this study reveal that CD11c expression does not correlate with response to TNF inhibitor biologics when tested for within pre-treatment whole blood samples of rheumatoid arthritis patients.
authors.affiliation: Arthritis Research UK, Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, the University of Manchester, Manchester, UK. samantha.smith-4@postgrad.manchester.ac.uk.
authors.forename: Samantha Louise
authors.initials: SL
authors.lastname: Smith
authors.affiliation: Arthritis Research UK, Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, the University of Manchester, Manchester, UK. steve.eyre@manchester.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.affiliation: Arthritis Research UK, Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, the University of Manchester, Manchester, UK. annie.yarwood@manchester.ac.uk.
authors.forename: Annie
authors.initials: A
authors.lastname: Yarwood
authors.affiliation: Arthritis Research UK, Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK. Kimme.Hyrich@manchester.ac.uk.
authors.forename: Kimme
authors.initials: K
authors.lastname: Hyrich
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK. mrpawm@leeds.ac.uk.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Morgan
authors.affiliation: UCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland. a.g.wilson@sheffield.ac.uk.
authors.forename: A G
authors.initials: AG
authors.lastname: Wilson
authors.affiliation: NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK. John.Isaacs@newcastle.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Isaacs
authors.affiliation: NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. darren.plant@manchester.ac.uk.
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.affiliation: Arthritis Research UK, Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, the University of Manchester, Manchester, UK. Anne.Barton@manchester.ac.uk.|NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Anne.Barton@manchester.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D039521:CD11c Antigen / Q000097:blood*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D015415:Biomarkers; D039521:CD11c Antigen; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept