Two single variants in immune system-related genes may help predict ankylosing spondylitis with active disease response to therapy.
Two pathways of the immune system, controlled by the chemokines (signaling molecules) interleukin 23 (IL-23) and IL-1, are known to play a role in ankylosing spondylitis.
Now, researchers investigated the potential diagnostic and predictive role of five natural variations, called single-nucleotide polymorphisms (SNPs), in genes related to the IL-23 pathway, as well as genes that are part of the IL-1 gene family.
A total of 431 patients with ankylosing spondylitis – 198 with active disease – and 206 age- and sex-matched healthy controls were recruited. Active disease was treated with standard nonsteroidal anti-inflammatory drugs, or inhibitors of tumor necrosis factor (TNF), for approximately 6 months.
Participants’ genome was analyzed for five SNPs related to the IL-23 pathway – IL-23R, IL-12B, TYK2, IL-6R, and IL-1R2 – in addition to the IL-1 cluster.
The analysis identified the IL-12B A and the IL-6R T allele variants (alleles are alternative forms of a gene that arise by mutation) as independent factors increasing the risk for ankylosing spondylitis, with patients showing higher frequencies of IL-12B AA and IL-6R TT alleles compared to age- and sex-matched healthy controls.
The IL-12B AA allele also correlated with higher disease activity and functional index score, according to the Bath Ankylosing Spondylitis Disease Activity and Bath Ankylosing Spondylitis Functional Index scores, respectively.
Researchers then moved on to assess the prognostic value of each variant for ankylosing spondylitis. They evaluated the Assessment of SpondyloArthritis international Society response (ASAS-20) as a readout for treatment effectiveness after approximately 6 months of treatment.
Patients with the IL-12B AA allele showed a higher ASAS-20 response, whereas those with IL-6R had a lower ASAS-20 response. These results suggested that the IL-12B and IL-6R gene variants could predict patients with active disease response to therapy.
Researchers performed further analysis and confirmed that the IL-6R T allele was an independent factor for worse ASAS-20 response in active ankylosing spondylitis patients. On the contrary, high levels of C-reactive protein – a marker of inflammation – predicted a higher ASAS-20 response.
Overall, these results reveal that IL-12B and IL-6R gene polymorphisms could serve as promising biomarkers for diagnosis and prognosis in ankylosing spondylitis patients.