Elevated levels of nitrotyrosine-modified protein adducts and their association with the severity of primary sjogren's syndrome and secondary sjogren's syndrome with rheumatoid arthritis in Taiwanese Patients.

OBJECTIVES

Primary Sjogren's syndrome (pSS) is an autoimmune condition characterized by glandular dysfunction. The roles of nitrotyrosine-modified (NT)-protein adducts and anti-NT-peptide adduct autoantibodies in disease progression and their potential as biomarkers remain underexplored. In this study, we assessed NT-protein adducts, related autoantibodies, and their associations with disease progression in pSS patients and their transformation into secondary SS with rheumatoid arthritis (RA-sSS).

METHODS

The serum levels of proteins, NT-protein adducts, and autoantibodies against novel pSS-specific component C3 (C3)914-926 and C4b-binding protein alpha chain (C4BPA)336-353 were analyzed via proteomics and immunoassays. The statistical significance of the odds ratios (ORs) was estimated. Biomarker combinations were assessed for diagnostic performance.

RESULTS

NT-protein adduct levels progressively increased across groups, reflecting increasing nitrosative stress. Elevated NT-protein adducts (OR = 4.542) and reduced levels of specific autoantibodies, such as IgA anti-C3914-926 (OR = 12.503), IgA anti-C3914-926 NT (OR = 12.758), IgA anti-C4BPA336-353 (OR = 15.962), IgM anti-C4BPA336-353 NT (OR = 2.471), and IgG anti-C4BPA336-353 NT (OR = 5.302), were identified as risk factors for disease progression in patients with pSS; in particular, NT-protein adducts (OR = 8.005) increased disease transformation to RA-sSS. LightGBM achieved the highest performance (AUC = 0.991) in distinguishing pSS from HCs, whereas XGBoost performed best (AUC = 0.876) in differentiating pSS from RA-sSS.

CONCLUSIONS

Our findings suggest that elevated NT-protein adducts may signify an increased risk for disease progression in pSS patients and transformation to RA-sSS. Machine learning integration of NT-protein adducts, autoantibodies, and traditional biomarkers may enhance early SS diagnosis. Key Points • The elevated nitrotyrosine-modified protein adducts may emerge as significant biomarkers of disease progression in pSS and its transformation into RA-sSS.. • The reduced specific autoantibodies, such as IgA anti-C3914-926, IgA anti-C3914-926 NT, IgA anti-C4BPA336-353, IgM anti-C4BPA336-353 NT, and IgG anti-C4BPA336-353 NT, were associated with increased risks of disease progression in pSS. • Integration of NT-protein adducts, autoantibodies, and traditional biomarkers enhances diagnostic accuracy for SS.