Orthotype: Next-generation orthopaedics

A unique set of genetic tests designed to improve patient management pre and post joint replacement surgery  

Approximately 15% of UK patients carry genes associated with increased reactivity to cobalt chrome implants

Orthotype Pre Op (blood sample in EDTA tube)
DNA is extracted using next generation sequencing technology and the patient's HLA DQ haplotype is identified. This haplotype is combined with patient age and sex to provide a patient specific risk profile to identify patients who are greater risk of developing an adverse immune response to a cobalt chrome implant.

Orthotype Post Op (blood sample in EDTA tube)
Adverse immune responses also depend on the performance of the implant. For patients who have a cobalt chrome implant which is in situ, we test not only for the HLA haplotype, but also for the concentrations of cobalt and chromium in the patient's blood. These results are then entered into the validated Orthotype algorithm and a report is sent to you indicating the presence or absence of an adverse response.

Orthotype Plus (blood sample in EDTA tube)
A blood test that identifies the same factors as Orthotype Post Op with the additional information of measurement of titanium concentrations in the blood. Measurement of titanium may help diagnose abnormal wear or loosening of titanium components where applicable.

Host Response
Studies consistently show that 10 to 25% of patients who receive a joint replacement may develop chronic pain.

There is an increasing amount of evidence to indicate poor clinical outcomes may be due to adverse immune responses to cobalt chrome.

Histologically confirmed signs of delayed type metal allergy (ALVAL) have been identified in between 7 and 44% patients undergoing revision of their TKRs.

This is some text insPerivascular Lymphocytic Infiltration Is Not Limited to Metal-on-Metal Bearings. Ng et al, Clinical Orthopedics and Related Research (2011)

Pseudotumors and High-Grade Aseptic Lymphocyte-Dominated Vasculitis-Associated Lesions Around Total Knee Replacements. Kurmis et al,
J Arthroplasty (2019).

The development and validation of the Orthotype tests are published in Nature Communications Medicine

The research underpinning Orthotype involved the collaboration of internationally recognised experts in the fields of surgery, pathology, genetics, molecular medicine, bioengineering and statistics.

Delayed type metal hypersensitivity was diagnosed through the examination of periprosthetic tissue specimens using peer reviewed methodology.

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement | Communications Medicine (nature.com)

Ortho Analysis

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.

Helping orthopaedic professionals create a complete patient picture with a comprehensive, easy to read report

We also recommend Orthotype before revision surgery to give the patient a greater chance of a successful outcome with their new prosthesis. Our Orthotype report is provided within 2 weeks of testing.

Orthotype Post Op
Combining the results of DNA testing and metal ion analysis, we can identify the likelihood of an active adverse reaction to metal debris.

Tailored decision making for long term gain. By predicting the likelihood of adverse immune responses, Orthotype can reduce the possibility of chronic pain and revision surgery.
10 to 25%
The incidence of sub optimal clinical outcomes following joint replacement surgery (sources: NJR, Rice et al, Beswick et al)

Helping surgeons make
better-informed decisions for the benefit of their patients

By giving surgeons a greater understanding of their patients as individuals, Orthotype can increase the chances of a positive outcome post operatively.

See our papers