title: Myeloid-related Protein 8/14 Levels in Rheumatoid Arthritis: Marker of Disease Activity and Response to Methotrexate.
abstract: OBJECTIVE
  Myeloid-related proteins (MRP) 8/14 belong to a family of calcium-binding proteins produced by myeloid cells. Baseline serum levels of MRP8/14 have been shown to predict response to biologicals in rheumatoid arthritis (RA). Because methotrexate (MTX) is the first-line therapy in RA, we studied whether MRP8/14 levels can predict response to MTX.
  
  
  METHODS
  Patients with active RA disease who were naive to disease-modifying antirheumatic drugs were enrolled. All patients were treated with MTX only, to a maximum of 25 mg/week or the maximal tolerated dose. At 4 months, the European League Against Rheumatism response was assessed. All patients who needed rescue therapy after 2 months or who did not respond at 4 months were classified as nonresponders.
  
  
  RESULTS
  Ninety patients were enrolled, of whom 3 discontinued MTX within 4-6 weeks, so 87 patients were analyzed [74 women, median (interquartile range; IQR) for the Disease Activity Score at 28 joints (DAS28) was 4.43 (4.1-5.1)]. The median (IQR) serum MRP8/14 level at baseline was 19.95 µg/ml (11.49-39.06). The serum MRP8/14 had good correlation with DAS28-C-reactive protein (CRP; r = 0.35, p = 0.001). The MRP8/14 levels fell significantly after 4 months of treatment (10.28 µg/ml, 5.95-16.05, p < 0.001). Among 87 patients, 69 were responders. The median (IQR) baseline level of MRP8/14 was higher among responders compared with nonresponders: 23.99 µg/ml (15.39-42.75) versus 9.58 µg/ml (6.11-24.93, p = 0.00250). The levels declined in the responders, from 23.99 µg/ml (15.39-42.75) to 10.41 µg/ml (5.83-15.61, p < 0.001), but not in the nonresponders, from 9.58 µg/ml (6.11-24.93) to 9.19 µg/ml (7.74-21.96, p = 0.687). Receiver-operation characteristic analysis showed that MRP8/14 was a better predictor of response than CRP and erythrocyte sedimentation rate, especially with early disease onset (< 1-yr duration).
  
  
  CONCLUSIONS
  MRP8/14 is a good marker of disease activity in RA, and higher levels predict response to MTX.
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.P.S. Patro, DM Senior Resident, MD Internal Medicine, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Singh, PhD Student, MSc Biotechnology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; R. Misra, Professor, FRCP, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Aggarwal, Professor, DM Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: Pradeepta Sekhar
authors.initials: PS
authors.lastname: Patro
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.P.S. Patro, DM Senior Resident, MD Internal Medicine, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Singh, PhD Student, MSc Biotechnology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; R. Misra, Professor, FRCP, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Aggarwal, Professor, DM Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: Ankita
authors.initials: A
authors.lastname: Singh
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.P.S. Patro, DM Senior Resident, MD Internal Medicine, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Singh, PhD Student, MSc Biotechnology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; R. Misra, Professor, FRCP, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Aggarwal, Professor, DM Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: Ramnath
authors.initials: R
authors.lastname: Misra
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.P.S. Patro, DM Senior Resident, MD Internal Medicine, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Singh, PhD Student, MSc Biotechnology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; R. Misra, Professor, FRCP, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences; A. Aggarwal, Professor, DM Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences. aa.amita@gmail.com amita@sgpgi.ac.in.
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood*; D040502:Calgranulin B / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D008727:Methotrexate
keywords: BIOMARKER; DRUG RESPONSE; INFLAMMATORY ARTHRITIS; METHOTREXATE; MRP8/14; RHEUMATOID ARTHRITIS