title: An immunological biomarker to predict MTX response in early RA.
abstract: OBJECTIVE
  The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis and appropriate therapeutic intervention. RA is associated with dysregulation of T-cell subsets (naïve, regulatory (Treg) and inflammation-related cells (IRC)) early in the disease. Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission with early treatment in RA.
  
  
  METHODS
  T-cell subsets were quantified in 108 drug-naïve, early RA patients commencing methotrexate (MTX) or MTX+antitumor necrosis factor (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28<2.6). A pilot study used frozen cells (38 patients and 35 HCs, see online supplementary material) and was validated with fresh blood (70 patients and 70 HCs).
  
  
  RESULTS
  Immune dysregulation in early RA was confirmed with an association between age and reduced naïve cells compared with HCs (p=0.006), a lower age-adjusted Treg and higher IRC frequency (p=0.001). Anticitrullinated peptide antibody (ACPA) positivity was associated with lower naïve (p=0.031) and Treg frequencies (p=0.039). In 50 patients treated with MTX, ACPA/age-adjusted analysis demonstrated that higher naïve cell frequency (relative to HC) was associated with remission (OR 5.90 (1.66 to 20.98), p=0.006, sensitivity/specificity 62%/79%, Positive Predictive Value (PPV)/Negative Predictive Value (NPV) 66%/76%). Remission with MTX+anti-TNF (n=20) was not found to be associated with naïve cell frequency, and for patients with reduced naïve cells the remission rate increased from 24% (MTX) to 42% (MTX+anti-TNF).
  
  
  CONCLUSIONS
  Baseline T-cell subset analysis has a value in predicting early RA remission with first therapy with MTX. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and help select the most appropriate therapy at disease presentation.
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Frederique
authors.initials: F
authors.lastname: Ponchel
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK Department of Rheumatology, University Hospital of Amiens, INSERM EA 4666, University Picardie Jules Verne, Amiens, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goëb
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Rekha
authors.initials: R
authors.lastname: Parmar
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Yasser
authors.initials: Y
authors.lastname: El-Sherbiny
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Boissinot
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Jehan
authors.initials: J
authors.lastname: El Jawhari
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Agata
authors.initials: A
authors.lastname: Burska
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Vital
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Harrison
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hensor
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Disease, The University of Leeds & the NIHR Leeds Musculoskeletal Biomedical Research Unit, The Leeds Trust Teaching Hospital, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D012074:Remission Induction; D012680:Sensitivity and Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: Naïve T-cell; regulatory T-cells Rheumatoid arthritis; remission