Immunopathology and molecular diagnosis of autoimmune bullous diseases

Abstract

Autoimmune bullous diseases are associated with autoimmunity against structural components maintaining cell–cell and cell matrix adhesion in the skin and mucous membranes. Pemphigus diseases are characterized by autoantibodies against the intercellular junctions and intraepithelial blisters. In pemphigoid diseases and epidermolysis bullosa acquisita, sub-epidermal blistering is associated with autoantibodies targeting proteins of the hemidesmosomal anchoring complex. The autoantigens in autoimmune blistering diseases have been extensively characterized over the past three decades. In general, the pathogenicity of autoantibodies, already suggested by clinical observations, has been conclusively demonstrated experimentally. Detection of tissue-bound and circulating serum autoantibodies and characterization of their molecular specificity is mandatory for the diagnosis of autoimmune blistering diseases. For this purpose, various immunofluorescence methods as well as immunoassays, including immunoblotting, enzyme-linked immunosorbent assay and immunoprecipitation have been developed. This review article describes the immunopathological features of autoimmune bullous diseases and the immunological and molecular tests used for their diagnosis and monitoring.

Blocking Fcα Receptor I on Granulocytes Prevents Tissue Damage Induced by IgA Autoantibodies

“…Aberrant deposits of IgA-Ag complexes are found in several chronic inflammatory diseases, including celiac disease, IgA nephropathy, Henoch-Schönlein purpura, IgA pemphigus, dermatitis herpetiformis, and linear IgA bullous disease (LABD) (6,(15)(16)(17). The latter two diseases are chronic skin diseases associated with IgA autoantibodies, which are characterized by subepidermal blisters with dense inflammatory infiltrates that are dominated by granulocytes.…”

“…Several molecular targets to which IgA autoantibodies are directed have been identified. For instance, anti-epidermal transglutaminase IgA autoantibodies are found in dermatitis herpetiformis (18), whereas IgA autoantibodies in LABD are directed against collagen XVII, also referred to as the bullous pemphigoid (BP) Ag of 180 kDa (BP180), which is a transmembraneous hemidesmosomal protein involved in maintaining cell-matrix adhesion in the skin (17,19). The potential of IgA autoantibodies to induce tissue damage and the pathogenic relevance of their interaction with granulocytes have, however, not yet been investigated in great detail.…”

Basement membranes and human disease

“…Epidermolysis bullosa acquisita is a rare acquired autoimmune subepidermal blistering disease of the skin, which derives its name from the similar phenotype to dystrophic EB (Mihai and Sitaru 2007;Woodley et al 2007). It is characterized by IgG autoantibodies against epitopes located in the NC1 domain of collagen type VII, the major component of anchoring fibrils.…”

Multiparametric autoimmune diagnostics: recent advances

“…4,44 Detection of tissue-bound or circulating autoantibodies against structural components maintaining cell-cell and cell-matrix interactions is essential for diagnosis of these diseases. 45 Again, the combination of screening on tissue, ie, esophagus and/or salt-split skin, with identification on antigen-specific substrates enables adequate detection of the relevant autoantibodies. 10 The antigens can be exposed in transfected cells, ie, the cell-based assay, or as antigen dots, all combined in the biochip IIF method.…”