Alopecia areata is characterised by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease-associated psychological morbidity.

Background: Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. Objectives To provide a detailed insight into the systemic cytokine signature associated with AA, and assess the association between cytokines and depression. Methods: Multiplex analysis of plasma cytokines from AA patients, psoriatic arthritis (PsA) patients and healthy controls. We also assessed incidence of depression and anxiety using the Hospital Anxiety and Depression Scale. Results: Our analysis identified a systemic inflammatory signature associated with AA, characterised by elevated levels of IL-17A, IL-17F, IL-21 and IL-23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL-33, IL-31 and IL-17E/25 are also significantly increased in AA. In comparison to PsA, AA was associated with higher levels of IL-17F, IL-17E and IL-23. We hypothesised that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. We assessed psychiatric comorbidity in AA using the Hospital Anxiety and Depression Scale and found that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL-22 and IL-17E are positively and significantly associated with depression. Conclusion: Our data highlight changes in both type 17 and 2 cytokines, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression.