Queensland researchers have improved the accuracy of ankylosing spondylitis (AS) testing by analysing thousands of genetic variants, rather than just looking at HLA-B27.
Queensland researchers have improved the accuracy of ankylosing spondylitis (AS) testing by analysing thousands of genetic variants, rather than just looking at HLA-B27.
AS risk is largely determined by genetics, but, until recently, testing for AS has been limited to a single variant – the HLA-B27 gene.
The new test, presented at the ACR/ARHP Annual Meeting in Chicago in October, analyses around 4,000 genetic variants found in European populations to calculate an AS risk score.
The AS test for the European population was based on around 7,700 AS patients and 14,000 controls.
The new test was significantly more accurate than HLA-B27 alone in European populations, with an AUC score of 0.92 compared with 0.87 for HLA-B27 and 0.9 for MRI. (AUC stands for area under curve: a score of 0.5 means that the model is no better at making predictions than a coin toss, and a score of 1 means the model makes perfect predictions.)
The researchers also developed a AS polygenic risk score based on East Asian-descent samples, which had an AUC of 0.95.
“Polygenic risk scores involving hundreds to many thousand single nucleotide polymorphisms capture a higher proportion of overall disease heritability and have greater discriminatory capacity and accuracy in disease-risk prediction,” the authors said.
The AS polygenic risk score was not yet commercially available, said Dr Zhixiu Li, the presenting author and a research fellow at the Queensland University of Technology’s Institute of Health and Biomedical Innovation. But the test would be an affordable option in the future, with a price tag of around $50, she said. (The HLA-B27 test currently costs around $40.)
Due to the limitations of current testing methods, people with AS are often diagnosed over a decade after the onset of symptoms and tend to miss out on treatment that could have improved their outcome.
The polygenic risk score overcomes some of these problems by having a higher specificity and sensitivity at an early stage in the diagnostic process.
“In early disease, MRI is the current gold standard for diagnosis, but it is very expensive, and many patients with early changes on an MRI scan don’t go on to get AS,” Dr Li said.
When the HLA-B27 result was combined with an MRI scan, the test was reasonably accurate. But early detection of AS was still somewhat challenging as not all people who were HLA-B27 positive developed AS.
“Thus, we think genetic profiling may be informative, particularly in early disease, but also potentially prior to onset of symptoms,” Dr Li said.
