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).

There is also an acquired type of EB called epidermolysis bullosa acquisita (EBA). EBA patients are born with normal skin and then during middle age, they inappropriately generate IgG antibodies against their C7 and AFs (Yaoita et al., 1981, Woodley et al., 1984;) leading to skin fragility, trauma-induced blisters and scarring reminiscent of hereditary RDEB. The conventional wisdom in Dermatology is that patients with genetic RDEB may have a clinical phenotype resembling EBA, but that they have no auto-antibodies against C7. In this study, we identified 22 patients with bona fide RDEB, and characterized their mutations and their disease phenotype clinically, pathologically, ultrastructurally and immunologically. We sought to determine if any of these RDEB patients had anti-C7 antibodies in their sera or skin.