Comprehensive Oxidative Stress Profiling and Clinical Correlates in Spondyloarthritis: The Role of Glutathione Peroxidase and Modifiable Lifestyle Factors

<b>Background:</b> Oxidative stress represents a key pathogenic factor in spondyloarthritis (SpA), yet its comprehensive assessment remains underutilized in routine clinical practice. <b>Objectives:</b> We evaluated oxidative stress biomarker profiles in SpA patients to determine associations with disease activity, systemic inflammation, structural damage, lifestyle factors, and therapeutic responses for practical clinical implementation. <b>Methods:</b> This cross-sectional study included 101 patients meeting the Assessment of SpondyloArthritis International Society (ASAS) 2009 criteria. Oxidative stress assessment utilized a validated biomarker panel: copper, zinc, glutathione peroxidase (GPx), ceruloplasmin (Cp), transferrin (TF), haptoglobin (Hp), bilirubin (BR), and uric acid (UA). Clinical, radiological, lifestyle, and therapeutic data underwent systematic analysis. <b>Results:</b> Glutathione peroxidase activity was elevated in 82.1% of patients, establishing it as the most sensitive oxidative stress marker. Copper levels increased in 30.7% and zinc deficiency occurred in 36.4% of cases. Oxidative stress markers correlated significantly with inflammatory parameters (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-monocyte ratio [NMR], systemic immune-inflammation index [SII]) and disease activity scores (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score based on CRP [ASDAS-CRP], Disease Activity Score 44 [DAS44-CRP]). Higher oxidative stress was associated with a poorer quality of life, as indicated by elevated Ankylosing Spondylitis Quality of Life (ASQoL) scores. Physical activity and adherence to a Mediterranean diet were independently associated with better antioxidant capacity. Smoking and nonsteroidal anti-inflammatory drug (NSAID) use correlated with increased oxidative burden. Anti-tumor necrosis factor alpha (anti-TNFα) therapy was associated with reduced levels of oxidative stress. Structural damage, particularly cervical spine involvement, correlated with heightened oxidative stress. <b>Conclusions:</b> This comprehensive evaluation reveals significant clinical correlations between oxidative stress and multiple disease domains in SpA. Modifiable lifestyle factors and therapeutic interventions have a significant impact on the redox balance. These findings establish practical targets for personalized management. The integration of oxidative stress assessment into routine practice could enhance disease monitoring and inform the development of antioxidant-based therapeutic strategies.