Background:

Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune blistering skin disease characterized by autoantibodies against type VII collagen, resulting in complement activation, neutrophil infiltration, and dermal–epidermal separation. Current therapies rely mainly on systemic immunosuppressants that often show limited efficacy and severe side effects. Preliminary results from our group demonstrated that treatment with angiotensin-(1–7) [Ang-(1–7)], a peptide of the protective arm of the renin–angiotensin system (RAS), reduced disease severity in the passive EBA mouse model, suggesting potent anti-inflammatory properties.

Beyond this, previous data of the passive EBA mouse model revealed time-of-day–dependent differences in disease severity, with higher disease severity following morning induction, and altered neutrophil recruitment patterns. As immune and inflammatory processes are tightly regulated by circadian rhythms, disturbances of this internal clock system may influence disease progression and severity.

Objectives:

(i) Replication of previous findings from the passive EBA model in the active model.

(ii) Determination of the therapeutic efficacy of Ang-(1–7) in the active EBA mouse model.

(iii) Characterization of alterations in the rest–activity cycle of EBA-affected mice.

(iv) Evaluation of the potential of Ang-(1–7) to restore altered circadian rhythmicity.

(v) Investigation of correlations between immunological parameters and circadian dysregulation.

Work program active EBA mouse model:

To analyze circadian regulation, locomotor activity will be continuously recorded using Rodent Activity Detectors (RADs). Flow cytometry, qPCR, immunofluorescence staining of tissue and microscopy will characterize immune cell infiltration, cytokine expression, and molecular markers linking Ang-(1–7) treatment to both inflammatory and circadian pathways.