Yu-Sheng Chang

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-C3^914−926 (OR = 12.503), IgA anti-C3^914−926 NT (OR = 12.758), IgA anti-C4BPA^336−353 (OR = 15.962), IgM anti-C4BPA^336−353 NT (OR = 2.471), and IgG anti-C4BPA^336−353 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-C3^914-926, IgA anti-C3^{914-926 NT}, IgA anti-C4BPA^336-353, IgM anti-C4BPA^336-353 NT, and IgG anti-C4BPA^336-353 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.

An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)^542–556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.

Coronary artery disease (CAD) is a global health issue. Lipid peroxidation produces various by-products that associate with CAD, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). The autoantibodies against HNE and MDA-modified peptides may be useful in the diagnosis of CAD. This study included 41 healthy controls (HCs) and 159 CAD patients with stenosis rates of 70%. The plasma level of autoantibodies against four different unmodified and HNE-modified peptides were measured in this study, including CFAH^1211–1230, HPT^78–108, IGKC^2–19, and THRB^328–345. Furthermore, feature ranking, feature selection, and machine learning models have been utilized to exploit the diagnostic performance. Also, we combined autoantibodies against MDA and HNE-modified peptides to improve the models’ performance. The eXtreme Gradient Boosting (XGBoost) model received a sensitivity of 78.6% and a specificity of 90.4%. Our study demonstrated the combination of autoantibodies against oxidative modification may improve the model performance.