Supplementary Material for: The role of reactive oxygen species in the pathogenesis of alopecia areata: a systematic review and meta-analysis.

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly
impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA
pathogenesis. However, the precise mechanism of this breakdown remains unclear. This
study investigates the potential role of reactive oxygen species in AA pathogenesis.

Summary: A systematic review and meta-analysis were conducted on observational studies and
randomized controlled trials from 2000 to 2024. Studies included AA patients and measured
oxidative stress index (OSI), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
peroxidase (GSH-Px), or paraoxonase-1 (PON1). Extracted data were analyzed using the
Cochrane risk-of-bias tool and random-effects models.The review included 21 studies with 743 AA patients. OSI was elevated in AA patients (effect size = 1.58, 95% CI [0.31–2.68], p = 0.00068). MDA levels were also elevated (effect size = 1.60, 95% CI [0.43–2.6], p = 0.00023), while SOD (effect size = -0.97, 95% CI [-1.65 to -0.30], p = 0.00066) and GSH-Px (effect size = -1.41, 95% CI [-2.28 to -0.53], p = 0.00068) activities were reduced. PON1 levels showed no significant difference (effect size = -3.56, 95% CI [-8.63 to 1.51], p = 0.051).

Key Messages: The elevated OSI, MDA, and decreased antioxidant activity in AA patients
suggest a substantial role for reactive oxygen species and oxidative stress in AA
pathogenesis, highlighting oxidative stress as a potential target for therapeutic intervention.
These results underscore the importance of oxidative stress in AA and support further research
into antioxidant-based therapies.