Chronic allergic diseases—including allergic asthma, allergic rhinitis, and atopic dermatitis—persist
as major global health burdens, characterized by recurrent inflammation, T-helper 2 (Th2) polarization,
elevated immunoglobulin E (IgE), and impaired immune tolerance. While current therapies provide
symptomatic relief, few address the upstream drivers of chronic immune dysregulation. Oxidative stress,
defined as a persistent imbalance between reactive oxygen/nitrogen species (ROS/RNS) and endogenous
antioxidant defenses, has emerged as a pivotal pathophysiological node. However, comprehensive
longitudinal evidence linking redox biomarkers, immune profiles, and clinical outcomes in large, diverse
cohorts remains limited, particularly in Southeast Asian populations with distinct environmental and
lifestyle exposures. This multicenter longitudinal experimental study enrolled 500 adults with chronic
allergic conditions across 12 Type B hospitals in Indonesia (January 2023–December 2025). Serial
assessments included serum malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-4,
IL-6, tumor necrosis factor-alpha (TNF-α), total IgE, disease severity scores, and quality-of-life indices.
Multivariate regression and structural equation modeling (SEM) were applied to disentangle direct and
indirect pathways. Elevated MDA (5.8 ± 1.2 nmol/mL; p < 0.001) and reduced SOD activity (1.9 ± 0.6
U/mL; p < 0.001) were strongly associated with increased Th2/pro-inflammatory cytokines and IgE.
SEM confirmed oxidative stress as a primary driver of immune dysregulation (β = 0.48; p < 0.001),
which in turn predicted greater severity (β = 0.41; p < 0.001) and poorer quality of life (β = −0.36; p <
0.001). These findings establish oxidative stress as a central upstream mediator of immune dysfunction
across major chronic allergic phenotypes, supporting the evaluation of redox-targeted interventions as
disease-modifying strategies.
