Natural Occurrence of Autoantibodies against Basement Membrane Proteins in Epidermolysis Bullosa

Antoni Gostyński,Gilles F.H Diercks,Maria-José Escamez,Nisha Suyien Chandran,Raúl De Lucas,Adela Garcia-Martin,Marcela Del Rio,Jeroen Bremer,Maria C Bolling,Alvaro Meana,Sara G Llames,Enno Schmidt,Ralf Ludwig,Marcel F Jonkman,Hendri H Pas,Anna M.G Pasmooij

doi:10.1016/j.jid.2021.10.030

Abstract

Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by lifelong trauma-induced blistering of the skin and mucosa and extracutaneous manifestations. Autoantibodies to a structural protein of the epidermal basement membrane zone (BMZ) such as dystonin (BP230), plectin, type XVII collagen (COL17/BP180), laminin-332, or type VII collagen (COL7) result in the same level of blister formation as in EB subtypes caused by mutations in their coding gene, such as in EB simplex (DST and PLEC), junctional EB (JEB) (COL17A1, LAMA3, LAMB3, or LAMC2), and dystrophic EB (DEB) (COL7A1) (Goletz et al., 2017; Has et al., 2020).

Highlights

Autoantibodies to a structural protein of the epidermal basement membrane zone (BMZ) such as dystonin (BP230), plectin, type XVII collagen (BP180/Col17), laminin-332 or type VII collagen result in the same level of blister formation as in Epidermolysis bullosa (EB) subtypes caused by mutations in their coding gene, such as in EB simplex (EBS) (DST and PLEC), junctional EB (JEB) (COL17A1, LAMA3, LAMB3, or LAMC2), and dystrophic
For the diagnosis of pemphigoid diseases Meijer et al recently proposed that direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) on salt split skin (SSS), and not enzyme-linked immunosorbent assay (ELISA) or blot, are essential and these techniques should be used to illustrate if pre-existing antibodies can bind to the skin (Meijer et al, 2019, Schmidt and Zillikens, 2009)
Since these data are missing in the literature, we have investigated skin biopsies and serum of 37 patients with EB with a wide variety of techniques, including DIF and IIF on SSS to assess the presence of circulating antibodies

Summary

TO THE EDITOR

Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by lifelong trauma induced blistering of the skin and mucosa, and extracutaneous manifestations. For the diagnosis of pemphigoid diseases Meijer et al recently proposed that DIF and IIF on SSS, and not ELISA or blot, are essential and these techniques should be used to illustrate if pre-existing antibodies can bind to the skin (Meijer et al, 2019, Schmidt and Zillikens, 2009). Serology revealed dermal binding of IgG in SSS and positive anti-Col autoantibodies in both ELISA’s consistent with a diagnosis of epidermolysis bullosa acquisita (EBA) (Figure 1, Table 1) Both patients did not report any noticeable change of skin phenotype that would indicate manifestation of EBA and in case of patient #29 his revertant skin patch did not blister, even after inducing mechanical trauma (mini skin rub test) (Figure 1B). In EB, the clinical significance of reactivity even in DIF and/or IIF on SSS remains uncertain

Jo ur na

On ur na iew ev re rR

Jo ro

Jo ly

Findings

Jo u