The article focuses on a patient who has been in stable remission for 4 years thanks to the treatment. The authors point out that his quality of life has significantly increased compared to the previous period, when he was on immunosuppressive anti-TNF therapy. He is experiencing better mobility and less pain. It is now possible to lead a more active lifestyle. The patient also stopped taking anti-TNF therapy after five years of continuous use.
A contribution to the project was made by Skoltech PhD student Kseniia Lupyr. According to Kseniia, she made the bioinformatic part of the work: “I have been analyzing T-cell repertoires for four years now. When I was doing my master’s degree, the first tests on primates were performed. I analyzed the results and confirmed that TRBV9+ T cells were removed, and no other T cells were affected. Later, I analyzed data from the first patient who received the new drug. I integrated all available information: lab test results, mobility metrics, sequencing data of T-cell repertoires; analyzed and visualized the results for the new paper. As the patient’s T-cell repertoires are available for 15 years, it’s possible to trace autoimmune clones over a long period of time. For example, we noticed that the patient’s well-being deteriorates with an increase in the proportion of autoimmune clones in the T-cell repertoire.”
According to Ksenia, targeted treatment for ankylosing spondylitis was achieved because, among other things, it is associated with human leukocyte antigen (HLA) B27. HLAs code for proteins that act as “showcases” on cell surfaces that show T cells what peptides are inside. Recognizing them, T-lymphocytes get activated and attack the corresponding cells of the body.
“Adaptive immune response varies between people. So different patients may have different autoimmune clones. Since the disease is associated with HLA B27, there is a chance that the drug will help many HLA-B27 positive patients with ankylosing spondylitis,” adds Ksenia. The authors of the paper also note that anti-TRBV9+ therapy may have applications in other HLA-B27 associated diseases, such as psoriatic arthritis, acute anterior uveitis, juvenile idiopathic arthritis, and Crohn's disease.
Clinical trials of the drug against ankylosing spondylitis are currently in the second phase, and the third one has recently been approved. Researchers are waiting for the results to draw conclusions about the drug’s effectiveness in a wider sample of patients.