Humoral and cellular autoimmunity in autoimmune bullous skin disorders

Autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullo us pemphigoid (BP), are severe, frequently life-threatening skin disorders. Immunologically, they are characterized by the presence of serum autoantib odies (auto-Ab) targeting distinct adhesion molecules of the epidermis or d ermoepidermal basement membrane zone. Antibody (Ab) binding interferes with the adhesive function of these molecules, leading to detachment and subseq uently blister formation. PV is the classical example of an Ab-mediated aut oimmune disease affecting epidermal adhesion. Auto-Ab against the desmosoma l adhesion molecule, desmoglein 3 (Dsg3), are critical in the pathogenesis of this disease, since the transfer of serum IgG Ab reactive with Dsg3 into newborn mice induces a bullous skin disease resembling PV. Autoreactive T cell responses to Dsg3 may be critical in the pathogenesis of PV because: ( 1) Ab production generally requires T cell help; (2) the involvement of CD4 + T lymphocytes in PV has been suggested by the strong association with dis tinct HLA class II alleles, and (3)T cell recognition of epitopes of Dsg3 m ay be crucial for the initiation and perpetuation of the production of Dsg3 -specific auto-Ab by B cells. In PV and BP, autoreactive CD4(+) T cells rec ognize distinct epitopes of the extra-cellular portions of Dsg3 and BP180 [ BP antigen 2 (BPAG2) or type XVII collagen], respectively, and produce pref erentially T helper type 2 (TH2) cytokines. Auto-Ab of the TH2-dependent Ig G4 subtype are preferentially seen in the active stages of both PV and BP, while auto-Ab of the TH1-dependent IgG1 subclass are predominant during the chronic course of these disorders. These observations suggest that autorea ctive TH2 cells may provide targets to specifically modulate the T cell-dep endent production of pathogenic auto-Ab in these disorders. Copyright (C) 2 000 S. Karger AG. Basel.