title: Elevation of circulating HLA DR(+) CD8(+) T-cells and correlation with chromium and cobalt concentrations 6 years after metal-on-metal hip arthroplasty.
abstract: OBJECTIVE
  Following metal-on-metal hip arthroplasty (THA), immunological reactions including changes in lymphocyte populations, aseptic loosening, and lymphocytic pseudotumors occur. We hypothesized that changes in lymphocyte subpopulations would be associated with elevated metal ion concentrations.
  
  
  METHODS
  A randomized trial involving 85 patients matched for age and sex and randomized to receiving metal-on-metal (n = 41) or metal-on-polyethylene total hip arthroplasty (n = 44) was conducted. 36 patients were eligible for follow-up after mean 7 (6-8) years. Concentrations of chromium and cobalt were analyzed by high-resolution inductively coupled plasma mass spectrometry. Leukocyte subpopulations and immunoglobulins in patient blood were measured using standard laboratory methods.
  
  
  RESULTS
  Patients with a metal-on-metal hip had higher serum concentrations of chromium (1.05 vs. 0.36 μg/L; p < 0.001) and cobalt (0.86 vs. 0.24 μg/L; p < 0.001) than those with metal-on-polyethylene. The percentage of HLA DR(+) CD8(+) T-cells was higher in the metal-on-metal group (10.6 vs. 6.7%; p = 0.03) and correlated positively with chromium and cobalt concentrations in patient blood (Pearson's correlation coefficient: 0.39, p = 0.02; 0.36, p = 0.03, respectively). The percentage of B-cells was lower in the metal-on-metal group (p = 0.01). The two groups were similar with respect to immunoglobulin concentrations and Harris hip scores, and there were no radiographic signs of loosening.
  
  
  CONCLUSIONS
  We conclude that immunological alterations appear to be associated with increased cobalt and chromium concentrations. It is tempting to speculate that HLA DR(+) CD8(+) T-cells are involved in the pathogenesis of allergic reactions, implant loosening, and lymphocytic pseudotumors.
authors.affiliation: Department of Orthopedics, Institute of Surgical Sciences, Uppsala University Hospital, Sweden. nils.hailer@surgsci.uu.se
authors.forename: Nils P
authors.initials: NP
authors.lastname: Hailer
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
authors.forename: Henrik
authors.initials: H
authors.lastname: Dahlstrand
authors.forename: André
authors.initials: A
authors.lastname: Stark
mesh_terms: D000328:Adult; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002857:Chromium / Q000097:blood; D003035:Cobalt / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000276:immunology; D006622:Hip Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000601:surgery; D020959:Polyethylene; D011446:Prospective Studies; D011474:Prosthesis Design; D011475:Prosthesis Failure; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006684:HLA-DR Antigens; D002857:Chromium; D003035:Cobalt; D020959:Polyethylene