Lymphocyte responses in patients with total hip arthroplasty

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 0.1 mM, 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 & 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‐γ (IFN‐γ) 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.