Year: 2026
Type: article
Study design: Observational Study
Abstract: The pathogenesis of acute rheumatic fever (ARF) is poorly understood, limiting the development of immune-modulating therapies to treat disease and prevent progressive heart damage. Here, participants with definite ARF were compared to other severe acute paediatric conditions and matched healthy controls by profiling circulating immune molecules and cells to inform disease mechanisms and potential druggable pathways. ARF shared immunological similarities with other inflammatory conditions, including elevated serum IL-6 and an increased frequency of circulating CD4+ T cells. However, elevation of the chemokine CCL5 and immunoglobulin IgG3, along with reduced expression of the chemokine receptor CXCR3 in the T cell compartment distinguished ARF from all other groups. Immunofluorescence imaging of rheumatic valve tissue confirmed a role for CXCR3-mediated T cell tissue homing during inflammatory disease. Together with a reduced frequency of circulating regulatory T cells, these data underscore a perturbed T cell compartment and provide a rationale for exploring currently available immune-modulating therapies to treat ARF. Acute rheumatic fever (ARF) is a serious sequela of Strep A infection, for which a diagnostic biomarker is still lacking. Here, the authors demonstrate that CXCR3 directs T cells to heart valves in patients with ARF, linking inflammation to tissue damage.
Source: Nature Communications
Authors: Francis M. Middleton, Reuben McGregor, Natalie Lorenz, Sarah Kilian, Anna E. S. Brooks, Saem Mul Park, Ciara Ramiah, Judith Tresidder, Timothy C. Barnett, Michael Serralha, William J. Martin, Florina Chan Mow, Glenn Pearson, Mark Mayo, David I. Broadhurst, Julie Bennett, Johann Brink, Nigel J. Wilson, Anna P. Ralph, Rachel H. Webb, P. Rod Dunbar, Jonathan Carapetis, Nicole J. Moreland
Institutions: University of Auckland, Maurice Wilkins Centre, Starship Children's Health, Health New Zealand, The Kids Research Institute Australia, The University of Western Australia, Charles Darwin University, Menzies School of Health Research, Edith Cowan University, University of Otago, Royal Darwin Hospital, Princess Margaret Hospital for Children, Perth Children's Hospital
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7146956073