title: In vitro reactivity to implant metals demonstrates a person-dependent association with both T-cell and B-cell activation.
abstract: Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. We initially hypothesized that metal-induced lymphocyte proliferation responses to soluble metal challenge (ions) are mediated exclusively by early T-cell activation (not B-cells), typical of a delayed-type-hypersensitivity response. We tested this by comparing proliferation (6 days) of primary lymphocytes with early T-cell and B-cell activation (48 h) in three groups of subjects likely to demonstrate elevated metal reactivity: group 1 (n = 12) history of metal sensitivity with no implant; group 2a (n = 6) well performing metal-on-metal THRs, and group 2b (n = 20) subjects with poorly performing metal-on-polymer total joint arthroplasties (TJA). Group 1 showed 100% (12/12) metal reactivity (stimulation index > 2) to Ni. Groups 2a and 2b were 83% (5/6) and 75% (15/22) metal reactive (to Co, Cr, or Ni), respectively. Of the n = 32 metal-reactive subjects to Co, Cr, or Ni (SI > 2), n = 22/32 demonstrated >2-fold elevations in % of T-cell or B-cell activation (CD25+, CD69+) to metal challenge when compared with untreated control. 18/22 metal-activated subjects demonstrated an exclusively T-cell or B-cell activation response to metal challenge, where 6/18 demonstrated exclusively B-cell activation and 12/18 demonstrated a T-cell only response, as measured by surface activation markers CD25+ and CD69+. However, there was no direct correlation (R(2) < 0.1) between lymphocyte proliferation and % T-cell or B-cell activation (CD25+:CD69+). Proliferation assays (LTT) showed greater ability to detect metal reactivity than did subject-dependent results of flow-cytometry analysis of T-cell or B-cell activation. The high incidence of lymphocyte reactivity and activation indicate that more complex than initially hypothesized immune responses may contribute to the etiology of debris-induced osteolysis in metal-sensitive individuals.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois 60612, USA. nhallab@rush.edu
authors.forename: Nadim James
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Marco
authors.initials: M
authors.lastname: Caicedo
authors.forename: Rachel
authors.initials: R
authors.lastname: Epstein
authors.forename: Kyron
authors.initials: K
authors.lastname: McAllister
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Jacobs
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D001672:Biocompatible Materials / Q000494:pharmacology*; D001826:Body Fluids / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007595:Joint Prosthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008670:Metals / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D019736:Prostheses and Implants; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D008670:Metals