Immunotherapeutic strategy to prevent progression and complications of acute rheumatic fever
Lepletier, A.; Rafeek, R. A. M.; Ketheesan, N.; Good, M. F.; Pandey, M.
Show abstract
Acute rheumatic fever (ARF) is an autoimmune disease triggered by antibodies and T-cells targeting the Group A streptococcal (GAS, Strep A) bacterium, often leading to rheumatic heart disease (RHD). Long-term antibiotic therapy is recognized as a cornerstone of public health programs to prevent reinfection and progression of ARF. However, better tools to slow disease progression, and mitigate its lifelong consequences are required. Evidence obtained in a preclinical model suggests that this can be achieved. Using the rat autoimmune valvulitis model, we explored the potential of low-dose interleukin 2 (LD-IL-2) as an immunotherapeutic intervention. In this model injection of recombinant Strep A M5 protein (rM5) to Lewis rats induce autoimmune complications, cardiac tissue inflammation and conduction abnormalities. In animals injected with rM5 and treated with LD-IL-2, no cardiac functional or histological changes were observed. LD-IL-2 therapy effectively reduced the production of cross-reactive antibodies against cardiac tissue and induced a significant increase in classical regulatory T-cells (Treg) and CD8+ Tregs in the mediastinal (heart-draining) lymph nodes. These novel findings suggest LD-IL-2 will be an effective immunotherapeutic agent for treating ARF/RHD.
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