Prevalence of specific anti-skin autoantibodies in a cohort of patients with inherited epidermolysis bullosa

Abstract

BackgroundInherited epidermolysis bullosa (EB) is a group of skin diseases characterized by blistering of the skin and mucous membranes.There are four major types of EB (EB simplex, junctional EB, dystrophic EB and Kindler syndrome) caused by different gene mutations. Dystrophic EB is derived from mutations in the type VII collagen gene (COL7A1), encoding a protein which is the predominant component of the anchoring fibrils at the dermal-epidermal junction.For the first time in literature, we have evaluated the presence of anti-skin autoantibodies in a wider cohort of patients suffering from inherited EB and ascertained whether they may be a marker of disease activity.MethodsSera from patients with inherited EB, 17 with recessive dystrophic EB (RDEB), 10 with EB simplex (EBS) were analysed. As much as 20 patients with pemphigus vulgaris, 21 patients with bullous pemphigoid and 20 healthy subjects were used as controls.Anti-skin autoantibodies were tested in all samples with the Indirect Immunofluorescence (IIF) method and the currently available ELISA method in order to detect anti-type VII collagen, anti-BP180 and anti-BP230 autoantibodies.ResultsThe mean concentrations of anti-type VII collagen autoantibodies titres, anti-BP180 and anti-BP230 autoantibodies were statistically higher in RDEB patients than in EBS patients.The sensitivity and specificity of the anti-type VII collagen ELISA test were 88.2% and 96.7%. The Birmingham Epidermolysis Bullosa Severity score, which is used to evaluate the severity of the disease, correlated with anti-skin autoantibodies titres.ConclusionsThe precise pathogenic role of circulating anti-skin autoantibodies in RDEB is unclear. There is a higher prevalence of both anti-type VII collagen and other autoantibodies in patients with RDEB, but their presence can be interpreted as an epiphenomenon.

Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

“…Our findings extend what was reported by Tampoia et al who, studying serum concentrations of BP180, BP230 and COL7 antibodies, found that the levels were significantly higher in patients with RDEB than in EBS patients, and the values were correlated with EB severity [12]. In our study population, in addition to antibodies against BP180, BP230 and COL7, antibodies against DSG1 and DSG3 were evaluated.…”

“…Several hypotheses have been proposed to explain why, in inherited EB, an autoimmune mechanism aggravates the basal disease [12], but the precise triggers for the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic autoimmune responses remain undefined. Considering that children with the more severe EB phenotype usually have a greater number of skin infections, it could be supposed that an altered microbial diversity may cause a worsening of skin inflammation and autoimmunity.…”

“…First, some cases of EB are complicated by autoimmune extracutaneous diseases [6,7,8,9,10,11]. Moreover, in several patients with EB, high levels of anti-skin antibodies, proportional to the severity of the disease, could be found [12,13]. Finally, a significant cytokine imbalance was demonstrated in EB, suggesting the presence of a systemic inflammatory disorder [13].…”

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita

“…ELISAs for Col7 are not highly specific as they may be positive in patients with Crohn disease or ulcerative colitis without cutaneous manifestations of EBA, atypical AIBD and patients with recessive dystrophic EB (RDEB) (Tables S5 and S6). Of note, the presence of circulating autoAbs against BP180, laminin 332 and the p200/laminin γ1 chain (detected by IB or ELISA), which may occur as a result of the epitope spreading phenomenon, does not rule out a diagnosis of EBA (supplementary cases 2 and 4 in Appendix S2). …”

Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

“…We were intrigued by the presence of collagen VII in lymphoid conduits and strived to understand its function. The previously reported elevated humoral immunity in RDEB (32,33), together with the observation that the T-cell areas in spleen were devoid of collagen VII, suggested that absence of collagen VII may cause a specific impairment of innate antibacterial immunity. In the conduit basement membrane, collagen VII would interact with laminin 332 and collagen IV (SI Appendix, Figs.…”