Utility of mimicking B cell epitopes between Mycobacterium leprae and host as prognostic biomarkers in type 1 reaction in leprosy

Mycobacterial infections such as leprosy and tuberculosis can induce autoimmune responses by disrupting host immune homeostasis. We previously identified eight mimicking B cell epitopes (BCEs) with elevated autoantibody levels in Type 1 Reaction (T1R). In this study, we longitudinally evaluated BCE-specific antibody responses and standardized a dot blot assay for T1R detection. A total of 150 untreated leprosy patients were enrolled: 50 each with T1R, Type 2 Reaction (T2R), and non-reactional (NR) cases; however, follow-up of T2R patients was not feasible. Patients were monitored every 3-4 months for changes in antibody profiles. ELISA quantified antibodies against 15 BCEs derived from Mycobacterium leprae (M. leprae) (HSP65, 50 S ribosomal protein, lysyl tRNA synthetase) and host proteins (keratin, myelin basic protein). Dot blot analysis was performed with pooled sera from each group, and cut-off values were derived from NR intensities. Elevated antibodies against HSP2, HSP4-HSP6, KER1, KER2, KER4, MBP50SB1, and MBPLMB2 were strongly associated with T1R and correlated with disease progression in longitudinal analyses. Blot analyses confirmed higher intensities in T1R and T2R compared to NR and healthy controls (HC). Furthermore, future studies with larger longitudinal cohorts and longer follow-up periods are needed to validate these findings and to better characterize changes in autoantibody levels throughout disease progression and treatment, while the identification of these BCEs as potential prognostic biomarkers may also support the adaptation of the dot blot assay into cost-effective lateral flow platforms for clinical screening.