title: Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study.
abstract: OBJECTIVE
  The dietary thiol compound and erythrocyte ingredient ergothioneine (ET) is the preferential physiological substrate of the organic cation transporter OCTN1, found to be associated with rheumatoid arthritis (RA) in genetic studies, but the biological roles of ET and OCTN1 are unclear. We investigated the association between ET concentrations in peripheral blood erythrocytes and the occurrence of RA.
  
  
  METHODS
  Erythrocyte ET concentrations in patients with mildly active RA (n = 73) were compared to ET levels in patients with coronary heart disease (CHD; n = 62) and osteoarthritis (OA; n = 148), serving as non-RA chronic inflammatory disease controls. Correlation of ET levels in erythrocytes with levels of ET and OCTN1 mRNA in CD14+ monocytes was determined in 10 healthy subjects.
  
  
  RESULTS
  Erythrocyte ET levels were significantly higher in patients with RA, with a median (interquartile range) of 12.6 micromole/l of erythrocytes (IQR 8.1-18.3), compared to 7.7 (IQR 5.0-12.0; p < 0.001) in CHD and 7.8 (IQR 4.8-12.8; p < 0.001) in OA. The prevalence of RA compared to non-RA controls increased with increasing blood ET concentrations, with an odds ratio of 0.23 (95% CI 0.13-0.41; p < 0.001) in the lowest quartile of RA erythrocyte ET levels to 3.11 (95% CI 1.54-6.29; p = 0.002) in the highest quartile. The group differences in ET values were maintained after adjustment for disease-related anthropometric and clinical variables (age, sex, body mass index, smoking, duration of disease, hemoglobin, C-reactive protein, and medication) and were also independent of erythrocyte glutathione levels and of polymorphisms of the OCTN1 gene. ET levels in erythrocytes were linearly correlated with ET concentrations (R2 = 0.936, p < 0.001) and OCTN1 mRNA levels (R2 = 0.946, p < 0.001) in CD14+ cells.
  
  
  CONCLUSIONS
  Mildly active cases of RA are associated with an unexplained high level of ET in red blood cells.
authors.affiliation: Department of Pharmacology, University Hospital of Cologne, D-50931 Cologne, Germany. dirk.taubert@medizin.uni-koeln.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Taubert
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazar
authors.forename: Gundula
authors.initials: G
authors.lastname: Grimberg
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert
authors.forename: Karl-Stefan
authors.initials: KS
authors.lastname: Delank
authors.forename: Andreas
authors.initials: A
authors.lastname: Perniok
authors.forename: Erland
authors.initials: E
authors.lastname: Erdmann
authors.forename: Edgar
authors.initials: E
authors.lastname: Schömig
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D016022:Case-Control Studies; D004880:Ergothioneine / Q000097:blood*; D004912:Erythrocytes / Q000737:chemistry* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D027701:Organic Cation Transport Proteins / Q000097:blood; D027981:Symporters
chemical_list: D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters; D004880:Ergothioneine