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", Cof7, Ni+' at 0.1 mM, and Ti+4 at 0.001 mM) in six subject groups: Group la = young controls, Group 1 b = 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 la & 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-y (IFN-y) 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.

Metal-on-metal hip resurfacing arthroplasty: A review of periprosthetic biological reactions

“…The possible role of metal-specific adaptive immune response in the pathogenesis of poor implant performance such as aseptic osteolysis has been investigated by Hallab et al (2005). The authors measured the lymphocyte responses to implant metals (Cr 3+ , Co 2+ , and Ni 2+ at 0.1 mM and Ti 4+ at 0.001 mM) in 6 subject groups: group 1a, young controls; group 1b, age-matched controls; group 2a, subjects with a history of OA and no history of metal sensitivity; group 2b, OA subjects with a history of metal sensitivity; group 3a, THA subjects with no or mild osteolysis; and group 3b, THA subjects with moderate osteolysis.…”

Titanium uptake, induction of RANK‐L expression, and enhanced proliferation of human T‐lymphocytes

“…7 Immune reactions to dermal contact and ingestion of metals, manifested as skin conditions such as eczema, urticaria, erythema, and pruritis, are believed to be of a type IV cell-mediated hypersensitivity. 8 Currently, the role of T-lymphocytes in the systemic and peri-implant tissue responses, characterized by increased osteolysis and implant failure (aseptic loosening) in patients with metallic orthopedic devices, remains poorly understood, with several conflicting studies regarding their actual involvement. 9 Pure titanium and titanium alloys are commonly used biomaterials in trauma and orthopedic surgery (wrist and acetabular prosthesis of a total hip arthroplasty).…”

Bio‐corrosion of stainless steel by osteoclasts—in vitro evidence

“…1 However, their permanent tendency to corrode when exposed to a physiological environment remains a serious concern. [2][3][4] Elevated concentrations of metal ions have been measured in clinically retrieved peri-prosthetic tissues, distal organs, and body fluids in total hip arthroplasty patients. [5][6][7] The biology behind corrosion inside the human body and the distribution of the metal ions throughout the organism is not fully understood.…”

“…It has been suggested that extracellular body fluids have corrosive proprieties and contain metal binding proteins. 2,3 Furthermore, it has been debated whether osteoclasts (OC) are able to corrode pure metal when entering into contact with metal surfaces. However, direct evidence of metal corrosion by OC has been missing to date.…”