Background: Acute Rheumatic Fever (ARF) is a severe autoinflammatory disease that can develop after a Streptococcus A (Strep A) infection in susceptible children and is a stark example of health inequality in New Zealand. Disease pathogenesis remains poorly understood, and this contributes to a current lack of specific therapies and treatments. We previously showed that immunoglobulin subclass 3 (IgG3) and complement component 4 (C4) were significantly elevated above clinical reference ranges in >90% of ARF patients and that IgG1, IgG3, IgA and C4 were able to distinguish ARF patients from matched healthy controls.
Methods: Concentrations of 20 circulating cytokines and the four previously identified immune features were determined using bead-based multiplex assays in an expanded cohort comprising 60 ARF cases, 30 Strep A pharyngitis and 30 healthy controls recruited within large-scale case-control studies in New Zealand.
Results: The results corroborate earlier findings with IgG1, IgG3, IgA and C4 significantly elevated in ARF patients compared to matched healthy and Strep A pharyngitis controls. Furthermore, significant elevation of IL-6, IL-7, TNF-a and APRIL were observed in ARF patients, while IP-10 elevation was associated with Strep A pharyngitis.
Conclusion: While IL-6 and TNF-a have previously been associated with ARF, the identification of lymphocyte growths factors IL-7 and APRIL provides new insight into ARF immunopathogenesis. Correlations and cluster analysis highlight the interplay between immune features in this expanded disease signature, which may help identify targets for immune-modulating drugs or immune-based therapies for ARF in the longer term.