title: Lymphocyte responses in patients with total hip arthroplasty.
abstract: How lymphocyte-mediated metal sensitivity affects orthopaedic implant performance remains poorly understood. Do patients with implants exhibit elevated lymphocyte reactivity to metals and is this reactivity more generalized or more implant-alloy specific? We investigated these questions by measuring lymphocyte responses to implant metals (Cr(+3), Co(+2), Ni(+2) at 0.1mM, and Ti(+4) at 0.001 mM) in six subject groups: Group 1a=young controls, Group 1b=age matched controls, Group 2a=subjects with osteoarthritis (OA) and no history of metal sensitivity, Group 2b=OA subjects with history of metal sensitivity, Group 3a=total hip arthroplasty (THA) subjects with no to mild radiographic osteolysis, and Group 3b=THA subjects with moderate osteolysis. Lymphocyte proliferation, using Lymphocyte Transformation Testing (LTT), and cytokine release provided quantitative reactivity measurement, where a stimulation index of >2 indicated metal sensitivity. OA subjects with a history of metal sensitivity (Group 2b) were more metal reactive to Ni than any other group, as expected (66% incidence and Stimulation Index >20). However, THA subjects (Groups 3a and b) were >3 fold more reactive to Cr (p<0.04), than were controls (Groups 1a & b) or OA subjects (Groups 2a & b). THA subjects with moderate vs mild osteolysis (Group 3b vs 3a) were more reactive to Co (43% vs 0% incidence). Only osteolytic THA subjects demonstrated increased cytokine responses with >two-fold (p<0.05) increases in soluble interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) levels in response to Cr challenge. This elevated incidence and averaged level of lymphocyte reactivity supports a metal-specific adaptive immune response and suggests involvement in the pathogenesis of poor implant performance, e.g. aseptic osteolysis.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, 1653 W. Congress Parkway, Chicago IL 60612, USA. nhallab@rush.edu
authors.forename: Nadim James
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Shelley
authors.initials: S
authors.lastname: Anderson
authors.forename: Tiffany
authors.initials: T
authors.lastname: Stafford
authors.forename: Tibor
authors.initials: T
authors.lastname: Glant
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Jacobs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D002857:Chromium / Q000009:adverse effects / Q000032:analysis; D003035:Cobalt / Q000009:adverse effects / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009532:Nickel / Q000009:adverse effects; D010003:Osteoarthritis / Q000276:immunology / Q000601:surgery
chemical_list: D016207:Cytokines; D002857:Chromium; D003035:Cobalt; D009532:Nickel