title: Diagnostic utility of oxidative damage markers for early rheumatoid arthritis in non-smokers and negative anti-CCP patients.
abstract: BACKGROUND
  Besides the development of new markers and diagnostic criteria for rheumatoid arthritis (RA), many patients are still diagnosed after several years of symptoms. Oxidative stress markers are already increased at an early stage of RA. Our aim was to evaluate the additional diagnostic value of these markers.
  
  
  METHODS
  A case-control study was performed. Patients met the 1987 RA ACR criteria, less than 2 years of symptoms and no previous treatment with disease-modifying anti-rheumatic drugs (DMARD), steroids or vitamin E. Controls were selected from patient's relatives and matched (1:1) by gender, age, and current smoking habit. Oxidative damage markers were malonyldialdehyde (MDA), Lipid hydroperoxides (LOOH) and Carbonyl proteins (CP). Statistical analysis was performed in agreement with the STARD initiative.
  
  
  RESULTS
  Sixty-five RA patients without treatment and 65 healthy controls were included. LOOH, CP, antibodies against citrullinated peptides (anti-CCP) and rheumatoid factor (RF) were significantly higher in patients, and MDA higher in controls. The same results were obtained in the subgroups of patients who smoke or not, and in anti-CCP positive or negative. The diagnosis performance of traditional markers showed good specificity but low sensitivity. The addition of LOOH and CP increased the sensitivity and the area under the receiving operating characteristic (ROC) curve especially in non-smoking (66%) and negative anti-CCP (51%) patients.
  
  
  CONCLUSIONS
  The separate or combined addition of LOOH or CP to the traditional disease markers improved the diagnosis of RA, especially in non-smoking or negative anti-CCP patients.
authors.affiliation: Clinical Biochemistry Department, University Hospital Virgen Macarena, Sevilla, 41071, Spain. enriquemelguizo@yahoo.es.
authors.forename: E
authors.initials: E
authors.lastname: Melguizo
authors.forename: V
authors.initials: V
authors.lastname: Navarro
authors.forename: B
authors.initials: B
authors.lastname: Hernández
authors.forename: K
authors.initials: K
authors.lastname: Santos
authors.forename: T
authors.initials: T
authors.lastname: Arrobas
authors.forename: C
authors.initials: C
authors.lastname: Domínguez
authors.forename: F
authors.initials: F
authors.lastname: Navarro
authors.forename: C
authors.initials: C
authors.lastname: González
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010456:Peptides, Cyclic
chemical_list: D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide