Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

Abstract

In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.

Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

“…Interestingly, depletion of collagen-VII from immunodeficient mice (NSG mice) results in a less severe disease phenotype. Taken together, these studies emphasize the critical role played by the immune cells in exacerbating the disease condition (Esposito et al, 2016).…”

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

“…Moving towards RDEB patients, a study of Esposito and coll. demonstrated that circulating levels of antibodies against skin proteins and pro-inflammatory cytokines, in particular, IL-6, are significantly higher with respect to healthy controls, and correlate with disease severity [71]. Of note, IL-6 levels were significantly associated with EB extension (localized or generalized disease), disease severity and anti-skin antibodies levels [71].…”

Treatment of epidermolysis bullosa pruriginosa‐associated pruritus with dupilumab

“…IL‐31 is a known pruritogen; however, no correlation was observed between the IL‐31 haplotype and EBP . Patients with EB display increased IL‐1β, IL‐2, IL‐6, IL‐10, tumour necrosis factor‐β and interferon‐γ levels, which seem to be higher in recessive DEB and generalized forms than in dominant and localized subtypes . IL‐6 and IL‐12 levels were found to correlate with disease severity .…”