Background:Immunoglobulin G3 (IgG3) and prothymosin alpha (PTA) have recently been proposed as putative biomarkers for acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) respectively. However, studies of these markers have so far been limited to single populations and they have not been evaluated in unwell controls with alternate diagnoses.
Methods:We studied a cohort of 240 children or adults with ARF or RHD and 248 healthy or alternate diagnosis controls recruited in Pakistan. Focusing on serum obtained from samples from children and young adults aged 5-21 years attending hospital with September 2020, we classified the 30 suspected ARF cases using the 2015 Jones’ Criteria giving 15 definite cases (all recurrent) and 15 ARF possible (11 recurrent) not completely fulfilling the diagnostic criteria. We compared these to 12 individuals with alternate diagnoses with CRP > 1mg/dL and 14 individuals with CRP below this threshold. Finally, we included all four available samples from children with RHD without concurrent ARF giving a total sample of 60 individuals. IgG3 and PTA were measured in serum using bead assay and a sandwich ELISA kit respectively.
Result: Total IgG3 was significantly elevated in the definite ARF cases compared to both inflammatory (p=0.006) and non-inflammatory controls (p=0.015), and 13 (87%) of definite ARF cases had IgG3 above 1mg/mL.In contrast, PTA concentrations were similar across all five groups (p=0.56), irrespective of the presence or absence of an inflammatory state.
Conclusion: IgG3 but not PTA is a promising biomarker for ARF which would benefit from further evaluation.