Rheumatoid arthritis (RA) is a progressive autoimmune disease marked by the presence of anti-citrullinated protein antibodies (ACPAs), which serve as key diagnostic and prognostic biomarkers. Despite their clinical value, the heterogeneity in ACPA fine-specificity poses significant challenges for the development of accurate and individualized diagnostics.
Peptide-based tools are valuable in autoimmune profiling but often suffer from enzymatic degradation and poor pharmacokinetic properties. To address this, Sunflower Trypsin Inhibitor-1 (SFTI-1) has emerged as a promising scaffold peptide due to its rigid 14-residue bicyclic structure, stabilized by head-to-tail cyclization and a disulfide bridge (Luckett et al., 1999; Korsinczky et al., 2001). Its structure has enabled diverse biomedical applications, including protease inhibition and epitope presentation (De Veer et al., 2021; Franke et al., 2018).
Building on the previous work by Gunasekera et al.(1028) and Eriksson et al. (2023) , where citrullinated epitopes were grafted onto the SFTI-1 scaffold to selectively bind ACPAs, our current research expands this approach toward diagnostic method development. Specifically, we utilize these designed peptides to evaluate ACPA fine-specificity across individual RA patients. Using custom ELISA formats and peptide-based affinity purification, our study aims to dissect ACPA reactivity profiles at a patient-specific level.
Preliminary results demonstrate that these grafted peptides can distinguish ACPA subpopulations, offering insight into immune heterogeneity across patients. This patient-level resolution supports the development of precision diagnostic tools and may facilitate the stratification of RA subtypes for future therapeutic targeting. These findings highlight the translational potential of SFTI-1-based peptide scaffolds in advancing precision medicine approaches for autoimmune diseases.