Immune system involvement in metal hip implant failure

Osteoarthritis (OA) is the most common debilitating disease, especially in the elderly.Total Hip Replacement (THR) is a last resort treatment for hip OA and Metal-on-Metal (MoM) THR was used commonly for its durability. While this is an effective treatment for many, around 12% of hip implants were revised in 2012. MoM articulations had poor implant survival compared with non-MoM, displaying four times higher failure rate. Between 1997 and 2004, 652 hip replacement surgeries were undertaken in Norfolk using the Ultima TPS MoM THR system (DePuy) which resulted in a high rate of early implant failure (27.4% at year 7). One of the proposed reasons for MoM THR failure is the adverse reaction to metal wear debris and consequent immune system mediated osteolysis resulting in peri-prosthetic loosening. To understand the immune system involvement in metal hip implant failure, a cohort of OA patients were recruited with and without an Ultima implant. This study investigated; The Human leukocyte antigen (HLA) allelic variation and implant failure association. Determined the composition and frequency of immune cells and inflammatory markers in Norfolk cohort. And tested the metal particle impact on immune cells. These experimental approaches were utilised to elucidate whether the metal implant failure is a result of an inflammatory process. The genetic disposition to metal hip implant failure was tested by conducting HLA typing for 25 different alleles across three MHC class II loci which revealed a protective haplotype against implant failure being DQA1*01:02 - DQB1*06. The analysis of immune parameters showed that all patient groups had normal levels of immune cell composition and cytokine levels apart from the Ultima Asymptomatic group, suggesting a regulatory mechanism in place for metal hip implant survival. Analysis of metal particle effect on immune cells demonstrated that these particles are immune-reactive and results inmacrophage-initiated and lymphocyte-mediated failure mechanisms