Bone tired of treatment with drugs that suppress the whole immune system:
there's emerging evidence for treatment that creates antigen-specific tolerance.
This week kicked my butt, not least because it’s our second week back in school, and I got so predictably sick. But also, the research on Systemic sclerosis is vast and fascinating…but only when you’re able to physically keep your eyes open. For this reason, I took a short break from Scleroderma to read up on a new study. Normally, I avoid mouse studies—too depressingly far from on-the-ground changes in diagnostics and treatment for human autoimmune disease sufferers. That, and I do not know enough about mice studies to know how relatable particular mouse research is to human anatomy and physiology. But, sometimes I have to make an exception. This news article provides a splashy, readable account of the basics of this September 2023 research study on a process tested in mice.
The process alters an already-established autoimmune response to self-antigens by teaching the immune system not to attack a particular self-antigen. Just like in the study I reviewed last week, the mice in this study were experimentally altered to have Experimental Autoimmune Encephalitis, which is designed to simulate human Multiple sclerosis. The authors outline a method that binds a particular antigen (any structure that an antibody can react to) to a molecule, already identified to teach immune tolerance to self cell components, in the liver. This study shows that Experimental Autoimmune Encephalitis antigens linked to these teacher molecules suppresses the immune response of effector T cells and memory T cells specifically to the Experimental Autoimmune Encephalitis antigen. For reference, T cells are a type of lymphocyte, which is a type of white blood cell.
The authors think this may have broad applicability to different autoimmune diseases. In humans with Multiple sclerosis, for a theoretical example, a Myelin Basic Protein antigen (the building blocks of nerve coverings that fast track messages through the brain, which are damaged in Multiple sclerosis) could be paired with this teacher molecule to suppress T cell destruction of myelin. For another theoretical example, in humans with synovial joint inflammation associated with several rheumatic autoimmune diseases, an antigen on the cells of the synovial lining could be paired with this teacher molecule to suppress T cell destruction of the synovium. I could go on…
I’m captivated by the baseline consistency of the process—a teacher molecule that behaves predictably in suppressing T cell response to a specific antigen. That specific antigen is interchangeable—with the potential to be individualized for targeted treatment. There’s much research to be done, but the news article hints at possible human clinical trials in Multiple sclerosis and one related, preliminary trial in humans with Celiac disease.
For those who are new to AutoimmuneDx, I am currently writing posts based on reader-requests for more information and analysis on particular autoimmune diagnoses. I base my posts on the questions, concerns and—yes, feelings—that come up while completing a Diagnosis Description (you can read more about what goes into a Diagnosis Description here). Diagnosis Descriptions are designed to be a catalog of information that effectively describes and organizes the scientific evidence on autoimmune disease for people without a medical background. If you would like me to take a closer look at a particular diagnosis, please leave a comment below. If you don’t feel comfortable commenting publicly, email me at autoimmunedx@gmail.com. Because I have a curious mind and a medical background, I sometimes get too wrapped up in the weeds of autoimmune disease, so if you would like me to clarify a post, a concept, a word, or anything in-between, please don’t hesitate to leave a comment or send an email.
References
Murray JA, Wassaf D, Dunn K, Arora S, Winkle P, Stacey H, Cooper S, Goldstein KE, Manchanda R, Kontos S, Grebe KM. Safety and tolerability of KAN-101, a liver-targeted immune tolerance therapy, in patients with coeliac disease (ACeD): a phase 1 trial. Lancet Gastroenterol Hepatol. 2023 Aug;8(8):735-747. doi: 10.1016/S2468-1253(23)00107-3. Epub 2023 Jun 14. PMID: 37329900.
Tremain AC, Wallace RP, Lorentz KM, Thornley TB, Antane JT, Raczy MR, Reda JW, Alpar AT, Slezak AJ, Watkins EA, Maulloo CD, Budina E, Solanki A, Nguyen M, Bischoff DJ, Harrington JL, Mishra R, Conley GP, Marlin R, Dereuddre-Bosquet N, Gallouët AS, LeGrand R, Wilson DS, Kontos S, Hubbell JA. Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses. Nat Biomed Eng. 2023 Sep 7. doi: 10.1038/s41551-023-01086-2. Epub ahead of print. PMID: 37679570.