Antiplectin autoantibodies in subepidermal blistering diseases

Background Hemidesmosomal proteins may become targets of autoimmunity in subepidermal blistering diseases. Well-known recognized autoantigens are the intracellular plaque protein BP230, the transmembrane BP180 and its shed ectodomain LAD-1. Objectives To establish the prevalence of autoimmunity against plectin, another intracellular plaque protein, and to investigate its antigenic sites. Methods Two hundred and eighty-two patients with subepidermal blistering diseases, investigated by routine immunoblot analysis for possible antiplectin antibodies, were included in the study. Epitope mapping was performed using recombinantly produced overlapping plectin domains from the actin-binding domain to the rod domain. The COOH-terminal region of plectin was not included in the study. Results In 11 of 282 (3·9%) patients an immunoblot staining pattern identical to that of antiplectin monoclonal antibody HD121 was found. Affinity-purified antibodies bound back to normal human skin in a pattern typical for plectin, i.e. to the epidermal basement membrane zone as well as to keratinocytes in the epidermis, and to myocytes. No binding was seen to plectin-deficient skin of a patient with epidermolysis bullosa simplex with muscular dystrophy. Epitope mapping of the plectin molecule showed that the central coiled-coil rod domain is an immunodominant hotspot as 92% of the sera with antiplectin antibodies reacted with it. Most patients with antiplectin antibodies also had antibodies to other pemphigoid antigens. Conclusions Plectin is a minor pemphigoid antigen with an immunodominant epitope located on the central rod domain.