Okello-et-al-2026-A plasma protein biomarker signature that differentiates acute rheumatic fever from related clinical presentations-2

ARF is a systemic inflammatory condition triggered by Group A Streptococcus infection, with timely diagnosis critical to prevent Rheumatic Heart Disease. ARF pathogenesis is poorly understood and diagnosis is based on clinical criteria.

Here, we compared ARF cases and well-defined controls from two Uganda cohorts. We identified a 5-protein signature that discriminates ARF patients from clinically-similar conditions (receiver operating characteristic-area under the curve (ROC-AUC)=1.0, n=18 definite ARF vs n=9 known alternate diagnosis; ROC-AUC=0.97, n=18 definite ARF vs n=13 unknown alternate diagnosis), which retained very good diagnostic value in a validation cohort (ROC-AUC=0.83 n=26 definite ARF vs n=13 unknown alternate diagnosis).