Detection of antibodies against corrosion products in patients after CoCr total joint replacements

Abstract

Sensitivity to nickel, cobalt, and chromium is common among the general population. The identification of these sensitivities is generally by the detection of cell-mediated immunity. Detection of humoral immunity to these metals has rarely been undertaken because suitable assays are not available. To further our knowledge about the systemic humoral immune system response to weak hapten-syngeneic or allogeneic protein conjugates (corrosion and wear products of metallic orthopedic devices), a sensitive enzymelinked immunosorbent assay (ELISA) method for testing for antibody (humoral immunity) to metals was developed. Microtiter plates were coated with human serum albumin (HSA) or glutathione (GSH) and then conjugated with metal ions. Plates coated with HSA or GSH and without metal ions served as background controls. An indirect ELISA method was used to detect antibody binding. Patients bearing cobalt-chromium alloy devices were considered to be the most likely candidates as sources of antibody to metal and were used to document the usefulness of the test. Specificity of the test was documented by inhibition studies with these metal ions in the ELISA assay. The serum samples of 10 patients were screened for the presence of Cr-, Co-, or Ni-specific antibody at various periods up to 5.5 years after implantation of F-75 cobalt alloy total joint replacements. All patients had implants that were functioning well. The pre-and postimplantation humoral immune profiles of patients were determined and compared with each preimplantation control and with a pooled normal serum sample. This study presents evidence that metalprotein complex-specific antibodies can be detected. The clinical implications remain to be determined. 0 1994 John INTRODUCTIONMetal sensitivity among the general population is fairly common, with sensitivity to nickel being the most frequent, followed by cobalt and chromium. These sensitivities are generally of the cell-mediated type. In previously sensitized subjects, skin contact or systemic exposure can trigger cutaneous and/or systemic hypersensitivity reactions. Early studies on the possible relation between sensitivity to metal and *To whom correspondence should be addressed at: Department of Biomedical Engineering, 504 Wickenden, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7207. problems with total joint replacement aroused considerable interest. Since then, metal sensitivity has been implicated by some researchers as contributing to aseptic loosening and failure of joint prostheses, but the reports on the magnitude of the problem are contradictory.Elevated levels of cobalt, chromium, nickel, and titanium are found in the blood, urine, and tissue at implant and remote site of patients with Co-Cr and Ti-base alloy total joint replacement components. Metal ions may bind to tissue and interstitial fluid proteins as soon as they are released from the metallic ~ubstrate.~ Because albumin is the most abundant protein in serum and in interstitial tissue fluid, all the metals bi...

Systemic metal-protein binding associated with total joint replacement arthroplasty

“…Unfortunately, preventing metal contamination at the parts per billion level is quite challenging when using protein separation methods having greater resolution (e.g., high pressure liquid chromatography, anion exchange Table IV, and they vary from high range immunoglobulins (from ≈200 to ≈800 kDa) 29,30 to abundant midrange proteins such as albumin (≈67 kDa) 29,30 and transferrin (≈125 kDa). 31 While this is the first report of metal-protein binding in the serum of humans with metal containing total joint replacements, studies of metal-protein binding associated with biomaterial degradation were previously conducted.…”

Total knee arthroplasty in patients with hypersensitivity to metals

“…The patch testing has several limits, due to the skin reactivity being different from the response of the joint tissues [3,23]. Cellular reactions to a contact with metals may be analysed in different ways: LTT, ELISA, MIF, and confocal microscopy are the most addressed [18,35]. It is now reasonable to consider that these methodologies may together give a comprehensive determination of a hypersensitivity to metals [23].…”

Systemic and Local Tissue Response to Titanium Corrosion

“…The products of metallic implant corrosion behave as haptens generating a hypersensitive reaction that involves the release of inflammatory mediators, known as cytokines, and macrophage recruitment (Hallab et al, 2001;Jiranek et al, 1993;Yang & Merrit, 1994). It remains unclear to date whether it is the hypersensitivity to metal that causes implant failure or vice versa (Hallab et al, 2001).…”