Immunotherapy to prevent rheumatic heart disease

Dr Ailin Lepletier de Oliveira, Griffith University

Vanguard Grant - 2 Year

Years funded: 2025 - 2026

Investigating immunotherapy to prevent rheumatic heart disease progression

Acute rheumatic fever (ARF) is an autoimmune response triggered by infections with group A Streptococcus (GAS) bacterium. Repetitive infections with GAS result in exacerbation of the inflammatory process leading to irreversible damage of the cardiac tissue, which characterises rheumatic heart disease (RHD). Besides, over 30% of patients with ARF develop Sydenham's chorea, a neurobehavioral manifestation of ARF that usually occurs in association with cardiac symptoms.

In Australia, First Nations people are 20 times more likely to die from ARF/RHD compared to Non-First Nations people. 23% of RHD cases in people aged <35 years progress to cardiovascular complications or death within 8 years. Furthermore, the expected costs of management of patients with ARF/RHD in Australia by 2031 is estimated to be AUD$344 million. Specific therapy for AFR is not available. Although recurrence of ARF can be prevented with monthly administration of penicillin, this preventive strategy is fraught with many problems.

Preclinical model offers a path toward targeted therapy

Over the last few years, we have developed and characterised the unique preclinical laboratory model that mimics the autoimmune nature of cardiac and neurobehavioral complications observed in ARF/RHD. Using the Rat Autoimmune Valvulitis (RAV) model, we have demonstrated that low-dose-IL-2 (LD-IL-2) immunotherapy is able to prevent the progression of ARF and suppress the development of carditis. We will investigate the cellular and molecular mechanisms underpinning LD-IL-2 therapy efficacy in this model and further demonstrate proof-of-concept for the role of a key immune cells, known as regulatory T cells (Treg), in suppressing the autoimmune process that leads to irreversible heart damage. Evidence obtained from this preclinical project will provide comprehensive information to formulate a clinical immunotherapeutic regimen that could halt the progression of ARF into RHD in patients.