title: High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent-onset rheumatoid arthritis patients.
abstract: BACKGROUND
  We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients.
  
  
  OBJECTIVE
  To investigate whether serum levels of HP are associated with the response of 12 weeks MTX therapy in recent-onset RA patients.
  
  
  METHODS
  Sixty-nine active RA patients with recent onset (< 24 months) were treated with MTX. Clinical variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were tested at week 0 and week 12.
  
  
  RESULTS
  After 12 weeks of MTX treatment, 34.7% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints [DAS-28] ≤ 3.2 and decrease > 1.2) and all others (65.2%) were defined as non-responders. The baseline HP mRNA in PBMCs from non-responders is significantly higher than those in responders (P < 0.05). Similar to mRNA expression, non-responders showed significantly elevated serum HP levels at baseline (369.9 ± 159.8 mg/dL) compared to those in responders (255.3 ± 143.9 mg/dL) (P = 0.01). Serum HP levels were decreased significantly from 255.3 ± 143.9 mg/dL at baseline to 186.4 ± 108.5 mg/dL at week 12 (P = 0.04) in responders, but remained at high levels in non-responders.
  
  
  CONCLUSIONS
  High serum levels of HP at baseline are associated with inadequate response of 12 weeks MTX treatment in recent-onset RA patients. Further replication studies in larger samples are needed to validate HP as a potential predictive biomarker for response to MTX therapy in RA.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Dunming
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Youxuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chengyin
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Miaojia
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins; D012333:RNA, Messenger; D008727:Methotrexate
keywords: haptoglobin; methotrexate; rheumatoid arthritis