De Novo Anti-Type VII Collagen Antibodies in Patients with Recessive Dystrophic Epidermolysis Bullosa

Abstract

The two main layers of human skin are held together by structures at the dermal-epidermal junction (DEJ) called anchoring fibrils (AFs). Without properly functioning AFs, the adherence between the epidermis and dermis is compromised. Clinically, this translates into skin fragility and skin bullae. AFs are composed of type VII collagen (C7) that has a central triple helical domain (TH) flanked by a 145-kDa non-collagenous amino-terminal domain (NC1) and a 30-kDa carboxyl-terminal domain (NC2) (Burgeson et al., 1993). AFs and C7 are perturbed in recessive dystrophic epidermolysis bullosa (RDEB), a disease characterized clinically by skin fragility, skin bullae, scarring, and nail loss (Fine et al., 2008). RDEB is caused by mutations in the COL7A1 gene encoding C7. Over 700 mutations have been identified in DEB patients (Wertheim -Tysarowska et al., 2012). According to a recent consensus report, RDEB is classified as RDEB, severe, generalized (RDEB-sev, gen), RDEB, generalized, other (RDEB-O) and RDEB inversa (RDEB-I) (Fine et al., 2008).