Orthotype: Next-generation orthopaedics

Next-generation DNA sequencing

As patients move, particles are generated from the implant surfaces. These particles are then taken up by antigen-presenting cells where they are digested in the lysosome and broken down into their constituent peptides.

These peptides then compete to occupy the binding grooves of the major histocompatibility complexes (MHCs), which is a critical trigger to stimulating the patient's immune system.

By using next-generation gene sequencing, we can precisely identify a patient's MHC structures, and, therefore, determine the probability of an adverse reaction.

The MHC complex

The MHC complex is encoded by the human leukocyte antigen (HLA) genes.

And it is the three dimensional structure of these MHC complex that determines which peptides are more likely to be present on the cell surface.

However, certain peptide fragments have greater immunogenicity than others.

Peptide determination

If the peptide presented at the cell surface is recognised as foreign, lymphocytes may be activated to combat the antigen. This, in turn, sets off a chain reaction that results in fluid accumulation and tissue destruction.

Through genotyping, we can determine which peptides a patient is more likely to present.

Blood metal ion analysis

For patients who have already undergone joint replacement surgery, we use inductively coupled plasma mass spectrometry (ICP-MS) to measure the level of cobalt and chromium in the bloodstream. It is widely accepted a level of 7 micrograms per litre indicates an increased risk of an adverse reaction.

However, our research has shown that a significant number of patients may develop destructive tissue lesions at concentrations as low as 2 micrograms per litre.

Orthotype incorporates blood metal ion testing and high resolution genotyping to help identify the patients at greatest risk of adverse tissue responses.

As there can be a significant time delay in the appearance of inflammation following surgery, an Orthotype test report will also provide the clinician with a time-dependent risk profile.