Autoimmune dermatoses

Clinical information

Bullous autoimmune dermatoses are rare, blister-forming diseases of the outer skin and the adjacent mucous membranes. They are characterised by the formation of autoantibodies against structural proteins of the skin. These structural proteins establish the cell-to-cell contact in keratinocytes within the epidermis and the adhesion of the epidermis to the dermis. Bullous autoimmune dermatoses are divided into four main groups based on their target antigens and the localisation of the blisters:

• Pemphigus diseases: desmoglein 1 (Dsg1), desmoglein 3 (Dsg3), different plakins (mostly envoplakin)
• Pemphigoid diseases: BP180, BP230, laminin 332, P200
• Epidermolysis bullosa acquisita: collagen type VII
• Dermatitis herpetiformis: endomysium (tissue/epidermal transglutaminase), deamidated gliadin peptides (GAF-3X)

Diagnostics

A conclusive diagnosis of blister-forming autoimmune dermatoses requires the detection of both tissue-bound autoantibodies by direct immunofluorescence and circulating autoantibodies. The circulating specific autoantibodies against epidermal antigens (prickle cell desmosomes and epidermal basement membrane) in patient serum are detected using the indirect immunofluorescence test (IIFT) with tissue sections of primary oesophagus (or tongue). For further differentiation of autoantibodies against basement membrane structures, tissue sections of primate salt-split skin are used. Final diagnosis is based on a combination of the clinical picture with the detection of autoantibodies against the individual target antigens using IIFT, monospecific ELISA or immunoblot analyses.

Patients who suffer from bullous pemphigoid (BP) exhibit autoantibodies against BP180 and frequently also against BP230. The serum level of autoantibodies against BP180 correlates with the disease activity of BP, the serum level of autoantibodies against BP230 with the duration of the disease. Hence, the Anti-BP180-NC16A-4X ELISA (IgG) and the Anti-BP230-CF ELISA (IgG) are not only suited to reliably serologically identifying BP, but also to monitoring the activity of the disease before and during treatment and assessing the disease duration. Autoantibodies against desmoglein 1 and 3 are markers for pemphigus diseases. IIFT has proven valuable for detecting circulating autoantibodies in pemphigus. ELISA using recombinant desmoglein 1 and 3 offer the same sensitivity and specificity as IIFT. The anti-Dsg1 and -Dsg3 antibody levels measured correlate to a large extend with the severity and activity of the disease and the therapy success. The determination of autoantibodies against envoplakin contributes to diagnosis of PNP as well as differential diagnostic clarification. The determination of autoantibodies against collagen type VII confirms the diagnosis of EBA and enables the delimitation from other bullous autoimmune dermatoses.