Genetics and The Immune Response to Metal Debris

• Research type

  Research Study

• Full title

  Is There a Genetic Predisposition to the Development of ALVAL?

• IRAS ID

  227785

• Contact name

  David Langton

• Contact email

  djlangton22@yahoo.com

• Sponsor organisation

  Newcastle NHS trust

• Duration of Study in the UK

  0 years, 2 months, 2 days

• Research summary

  Is There a Genetic Predisposition to the Development of ALVAL?
  Metal on metal hip replacements were reintroduced globally at the turn of the century. Intended to more durable than conventional plastic hips, they were implanted mainly into younger patients. Unfortunately, complications have emerged secondary to adverse immune responses that patients have developed to metal debris (primarily composed of cobalt and chromium particles) generated from the hips.
  In response to these problems, in 2008 we began to examine the removed prostheses and compare the amounts of metal exposure to the cellular responses in the tissues retrieved from around the joints. There appear to be two general cellular responses. With massive metal exposure, the predominant cellular response is macrophagic, and the resulting injury is mostly limited to the bone. With intermediate levels of metal exposure, a cellular response (known as aseptic lymphocyte dominated vasculitis associated lesion (“ALVAL”)) can develop alongside the macrophagic infiltration. ALVAL is associated with the development of massive fluid effusions and widespread soft tissue injury. The risk factors for the development of ALVAL are poorly understood. Our ongoing investigations however have indicated that female and older patients more readily develop the condition. The cellular features of ALVAL are similar to autoimmune diseases such as rheumatoid and Crohn's disease. Over 500 patients have undergone revision surgery for failure of their devices at University Hospital of North Tees. We would like to conduct genetic testing (HLA typing) on tissues removed from 50 patients who developed ALVAL with tissues retrieved from 50 patients who did not. Our specific focus would be on determining whether there are similarities with other autoimmune diseases. The study would use tissues already retrieved from previous surgeries as part of routine clinical care and would be conducted in a fully anonymised fashion.

• REC name

  South Central - Oxford B Research Ethics Committee

• REC reference

  17/SC/0498

• Date of REC Opinion

  19 Sep 2017

• REC opinion

  Favourable Opinion