It is thought that metal ions from metal on metal bearing hip replacements cause DNA damage and immune dysfunction in the form of T cell mediated hypersensitivity. To explore the hypothesis that there is a relationship between metal ion levels and DNA damage and immune dysfunction in matched patient groups of hip resurfacings and standard hip replacements reflected in the levels of lymphocyte subtypes (CD3+ T cells, CD4+ T helper cells, CD8 +T cytotoxic/suppressor cells, CD16 +Natural Killer and CD19+ B cells) in peripheral blood samples, we analysed peripheral blood samples from 68 patients: 34 in the hip resurfacing group and 34 in the standard hip arthroplasty group. Samples were analysed for counts of each sub-group of lymphocyte and cytokine production. Whole blood cobalt and chromium ion levels were measured using inductively-coupled mass spectrometry. All hip components were well fixed.

Cobalt and chromium levels were significantly elevated in the resurfacing group compared to the hybrid group (p<0.001). There was a statistically significant decrease in the resurfacing group's level of CD8+ cells (T cytotoxic/suppressor) (p=0.010). No other subgroup of lymphocytes was significantly affected. Gamma interferon levels post antigen challenge were severely depressed in the hip resurfacing group.

A threshold level of blood cobalt and chromium ions for depression of CD8+ T cells was observed. Hip resurfacing patients have levels above this threshold whilst standard hip replacements fall below it. The patients all had normal levels of CD16 +Natural Killer and CD19+ B cells suggesting that this is not a bone marrow toxic effect. Cytokine analysis confirmed that some aspects of T cell function in hip resurfacing patients are severely depressed.

Introduction and aim: We have previously shown an association between whole blood metal ions and reduced CD8+ T cells in patients with unilateral metal on metal (MOM) hip resurfacings. Our aim was to substantiate this controversial finding with a follow up cohort of larger numbers of patients before further immunological investigation.

Method: We measured lymphocyte subset counts and whole blood Cobalt and Chromium in 2 groups of patients: a Birmingham hip resurfacing group (n=100); and a metal on polyethylene MOP hip arthroplasty group (n=34). Metal ions were measured using inductively-coupled mass spectrometry (ICP-MS) with a Dynamic Reaction Cell (DRC). The detection limit was 10 parts per trillion. All hip components were well fixed, clinically and radiologically.

Results: Cobalt and chromium levels were significantly elevated in the MOM resurfacing group compared to the MOP group (p< 0.0001). There was a statistically significant decrease in the MOM resurfacing groups’ level of CD8+cells (T cytotoxic) (p=0.005) when analysed by a Mann-Whitney U test. There was no significant difference between levels of CD4+ (T helper cells), CD19+ (B cells) and CD16/56+ (Natural Killer cells). A threshold level of blood cobalt and chromium ions for depression of total numbers CD8+ T cells was observed.

Conclusions: This follow up cohort of 100 MOM hip resurfacing patients has replicated the association of reduced CD8+ T cells and raised metal ion levels observed in our founder cohort. This was specific to CD8+ T cells. We are now more certain that this association needs further detailed immunological investigation.

Introduction and aim: We have previously shown suppressed levels of CD8+ T lymphocytes in patients with metal-on-metal (MOM) hip resurfacing compared to patients with metal on polyethylene hip replacements. Functional assessment of T lymphocytes may help to determine the importance of this CD8+ reduction following hip resurfacing.

Method: We isolated peripheral blood mononuclear cells (PBMC) from patients with unilateral MOM hip resurfacing (n=7) and healthy controls without hip replacement (n=8). Patients with hip resurfacing had excellent Harris Hip scores (mean 90) and well fixed components on radiographs. Whole blood and serum levels of Cobalt (Co) and Chromium (Cr) ions were measured with Inductively-Coupled Mass Spectrometry. T cell function was assessed by

cell proliferation assays (3H-thymidine incorporation) and

Results: Co and Cr ion levels were significantly elevated in the MOM hip resurfacing group compared to the control group (p< 0.001). Proliferation rates of T cells were comparable between the two groups over one week, but interferon-gamma (IFN-γ) production in the MOM hip resurfacing group was significantly decreased (p < 0.05), when compared to the control group.

Conclusion: IFN-γ is normally produced by CD8+ (T cytotoxic cells) and CD4+ (T helper 1 cells) in response to viral infection and high levels of IFN-γ is associated with autoimmune disease. Raised levels of metal ions from hip resurfacing reduces the production of IFN-γ following stimulation with PHA. This finding has been patented for potential therapeutic use through MRC technology.

Introduction: There have been 70,000 hip resurfacings implanted, predictions are for it to become 12% of the US hip replacement market by 2010 (Goldmann Sachs report Oct 2005). There is concern that the cobalt and chromium ions released from metal on polyethylene hip replacements cause immune dysfunction in the form of T cell mediated hypersensitivity (indicated by increased numbers and stimulation of T cells). If metal ions cause significant effects on white blood cells we might reasonably expect to detect this by simply measuring numbers of white blood cells.

Aim : To examine the possibility that raised metal ions may cause an abnormal number of white blood cells, termed a blood dyscrasia.

Method : Peripheral blood samples were analysed from 68 patients: 34 in the hip resurfacing group and 34 in the standard hip arthroplasty group. Samples were analysed for counts of each sub-group of lymphocyte. Functional assessment was also performed using a activation panel of white cell CD markers. Whole blood cobalt and chromium ion levels were measured using inductively-coupled mass spectrometry. All hip components were well fixed.

Results : Cobalt and chromium levels were significantly elevated in the resurfacing group compared to the hybrid group (p< 0.001). There was a statistically significant decrease in the resurfacing groups’ level of CD8⁺ cells (T cytotoxic/suppressor) (p=0.010). There was a characteristic pattern of immune modulation seen on the activation panel.

Conclusions : We found an immune modulation in patients with metal on metal hip resurfacing. This was not a hypersensitivity reaction. This change in T cell function may be detrimental or beneficial to patients.