Ankylosing spondylitis, or AS for short, is a form of arthritis that affects joints in the spine and pelvis, causing them to fuse together which results in severe pain and disability. The immune system plays an important role in AS and we know that drugs that shut down or inhibit parts of the immune system provide considerable symptom relief to patients including relief of pain. Until recently there were very few of these drugs available and patients were typically treated with the drug that best suited their clinical symptoms. However, new families of drugs are now available with more in development and the selection of which drug to use on which patient needs now to be better informed and to include an understanding of the patients’ immune profile. Our project studied groups of AS patients who have either responded well or poorly to treatment with two of these families of drugs, anti-TNF or anti-IL-17 monoclonal antibodies, to determine whether there are tell-tale ‘signatures’ in their immune or genetic profiles that could have predicted their treatment response.
We developed a sophisticated assay to study patient immune cell functions in detail. This uses a technique called flow cytometry which allows us to measure amounts of protein expressed in and on cells. Our flow cytometry assay has been designed to measure 28 key proteins that regulate immune cell functions. This assay was the applied to patient samples. The patients were selected from a biobank and were chosen as patients who had previously responded poorly to anti-TNF drugs and subsequently responded well to anti-IL-17 therapy. A second group of patients who responded well to anti-TNF treatment was also studied. In parallel measured expression of immune genes using a technique called RNA-sequencing. From our flow cytometry analysis we were able to determine an immune signature that segregates with patient drug responses. Analysis of our gene expression study is complex and will require further study to unlock its full potential. Overall, this pilot study suggests that study a patients immune cells may be an effective way of tailoring treatment options for AS.