Controlling Our Immune System — 11

Primary prevention of type 1 diabetes is a bigger challenge than intervening once the condition is manifest with considerable loss of β-cell mass and function. As with all autoimmune conditions, we must find the high-risk people, and at the earliest point possible in their lives. For type 1 diabetes, that can be helped by screening with autoantibodies, since only 15 percent of people who develop this disease have a family history. Some have advocated routine autoantibody screening to be done in children at two points, at ages three to five and eleven to thirteen years, but that hasn’t been initiated. Another way to assess risk is via genomics, which would antedate the appearance of autoantibodies if done early, be it polygenic risk scores that have been amply validated across ancestries or whole genome sequencing. Taking a polygenic risk score at birth has been advocated to guide the need for autoantibody testing. Particularly screening antigen-specific CD4 T cells or islet-reactive CD8+ cells could be used to detect high risk at very early stages before autoantibodies are manifest. A natural killer cell gene expression profile has also been shown to identify high-risk individuals. Accordingly, there is no shortage of ways that we can screen, integrate the data with multimodal AI, and be in a far better position to prevent this disease in the future.

Rheumatoid arthritis sufferers have new treatment options too. Abatacept is a fusion protein that works on the antigen-presenting cell (compared to the T cell as in type 1 diabetes with teplizumab), binding to its CD80 and CD86 receptors, to block T cell activation. It had already been shown to be helpful for treatment of rheumatoid arthritis but used in only 5 percent of patients. In a randomized trial of people at high risk, with presence of anti-citrullinated antibodies, joint pain without swelling, and signs of inflammation in MRI scans, all symptoms improved, and benefits persisted after six months of treatment. A second randomized trial that treated for twelve months compared with placebo showed similar results, but over the next twelve months, the efficacy waned. The results of these trials were deemed a substantial improvement over current treatments such as methotrexate and rituximab for autoantibody-positive arthralgia.