title: Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.
abstract: BACKGROUND
  To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries.
  
  
  METHODS
  A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE).
  
  
  RESULTS
  Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 - p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident.
  
  
  CONCLUSIONS
  The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value.
authors.affiliation: Department of Internal Medicine Faculty of Health Sciences, University of Pretoria, Bophelo Road, Private Bag X663, Pretoria, 0001, South Africa. mahmoodally@gmail.com.|Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Bophelo Road, Pretoria, 0001, South Africa. mahmoodally@gmail.com.
authors.forename: Mahmood M T M
authors.initials: MM
authors.lastname: Ally
authors.affiliation: Division of Rheumatology, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Chris Hani Road, Johannesburg, 2013, South Africa. drbridget@gmail.com.
authors.forename: Bridget
authors.initials: B
authors.lastname: Hodkinson
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Bophelo Road, Pretoria, 0001, South Africa. pieter.meyer@up.ac.za.|Tshwane Academic Division of the National Health Laboratory Service, Bophelo Road, Pretoria, 0001, South Africa. pieter.meyer@up.ac.za.
authors.forename: Pieter W A
authors.initials: PW
authors.lastname: Meyer
authors.affiliation: Biostatistics and Epidemiology Division, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, York Road, Johannesburg, 2193, South Africa. eustasius.musenge@wits.ac.za.
authors.forename: Eustasius
authors.initials: E
authors.lastname: Musenge
authors.affiliation: Department of Internal Medicine Faculty of Health Sciences, University of Pretoria, Bophelo Road, Private Bag X663, Pretoria, 0001, South Africa. grtintinger@gmail.com.|Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Bophelo Road, Pretoria, 0001, South Africa. grtintinger@gmail.com.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Tintinger
authors.affiliation: Division of Rheumatology, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Chris Hani Road, Johannesburg, 2013, South Africa. tikly.mohammed01@gmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Tikly
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Bophelo Road, Pretoria, 0001, South Africa. ronald.anderson@up.ac.za.
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D003906:Developing Countries; D004359:Drug Therapy, Combination; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D008727:Methotrexate