title: Circulating cell free DNA: a marker to predict the therapeutic response for biological DMARDs in rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA.
  
  
  RESULTS
  The concentration of ccfDNA in RA patients at baseline was higher than healthy controls (P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not (P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA (P = 0.00011).
  
  
  CONCLUSIONS
  After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.
authors.affiliation: Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.|Department of Rheumatology, Kobe Kaisei Hospital, Kobe, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Naonori
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakai
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kaneshiro
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Kohjin
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Rheumatology, Kobe Kaisei Hospital, Kobe, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Rheumatology, Kobe Kaisei Hospital, Kobe, Japan.|Department of Orthopedic Surgery, Kobe Kaisei Hospital, Kobe, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Shibanuma
authors.affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D001688:Biological Products / Q000627:therapeutic use*; D001799:Blood Sedimentation; D016022:Case-Control Studies; D000073888:Cell-Free Nucleic Acids / Q000097:blood* / Q000235:genetics; D004247:DNA / Q000097:blood* / Q000235:genetics; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D000073888:Cell-Free Nucleic Acids; D005819:Genetic Markers; D004247:DNA
keywords: biological DMARDs; cell-free DNA; response predictor; rheumatoid arthritis; synovial fluid