Epitope Spreading: Lessons From Autoimmune Skin Diseases

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Epitope Spreading: Lessons From Autoimmune Skin Diseases Lawrence S. Chan, Carol J. Vanderlugt, Takashi Hashimoto, Takeji Nishikawa, John J. Zone, Martin M. Black, Fenella Wojnarowska, Seth R. Stevens, Mei Chen, Janet A. Fairley, David T. Woodley, Stephen D. Miller, Kenneth B. Gordon Journal of Investigative Dermatology Volume 110, Issue 2, Pages 103-109 (February 1998) DOI: 10.1046/j.1523-1747.1998.00107.x Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Model of epitope spreading in chronic cell-mediated and antibody-mediated autoimmune diseases. The presentation of the primary (1°) epitope to the T helper cells (Th) leads to cell- or antibody-mediated tissue injury and release of a secondary (2°) “new” antigen (Ag) or 2° epitope of the same Ag. The presentation of the 2° epitope to the naive Th subsequently leads to the development of cell- or antibody-mediated autoimmunity against the 2° Ag (or epitope). APC, antigen presenting cells (Langerhans cells, macrophages, dendritic cells, B cells); Mac., macrophages; PC, plasma cells; Com., complements; PMN, polymorphic nuclear leukocytes; Eos., eosinophils; Lym. Tiss., lymphoid tissues; Prolif., proliferation; Differ., differentiation; MIPlα, macrophage inflammatory protein 1α; IFNγ interferon-γ; TNFβ, tumor necrosis β; LT, leukotriene; (+), help. (Vanderlugt and Miller, 1996.) Journal of Investigative Dermatology 1998 110, 103-109DOI: (10.1046/j.1523-1747.1998.00107.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Lichen planus associated with BP. Western blot analyses detected a 180kDa BP antigen recognized by the IgG autoantibodies from a patient affected with lichen planus (lane 2) who subsequently developed a new blistering disease with IgG autoantibodies that label the epidermal side of salt-split skin substrate. Controls include sera from two BP patients (lanes 1 and 3) and serum from a normal volunteer (lane 4). Journal of Investigative Dermatology 1998 110, 103-109DOI: (10.1046/j.1523-1747.1998.00107.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Psoriasis associated with BP. Clinical observation of new onset of BP in a patient with long history of psoriasis (a). Histopathology confirmed the diagnosis of BP in the blister (curved →) in association with psoriasis plaques (straight →). The diagnosis of BP was further documented by linear IgG deposition in the patient’s peri-blister skin BMZ and by patient’s circulating IgG autoantibodies that bound to skin BMZ (b) and recognized a 230kDa BP antigen by western blot [c, lane 2 was reacted with this patient’s serum, lanes 1 and 3 were reacted with sera from two BP patient controls, normal human serum showed negative reaction (not shown)]. Journal of Investigative Dermatology 1998 110, 103-109DOI: (10.1046/j.1523-1747.1998.00107.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Stevens—Johnson syndrome associated with cicatricial pemphigoid. Histopathology documented the occurence of primary Stevens— Johnson syndrome (a) that affected a patient who 6 mo later developed a secondary chronic inflammatory scarring ocular disease (b). At the time of acute episode of Stevens—Johnson syndrome, extensive eosinophilic necrosis of keratinocytes, prominent mononuclear cell infiltration, and hydropic degeneration of the basal keratinocytes were observed (a). At the time of chronic ocular disease, biopsy showed linear IgG (c) deposition at the basement membrane. The patient had a high titer (1:2560) of circulating anti-basement membrane IgG autoantibodies that recognized a 120kDa epidermal antigen (Chan et al, 1991). Journal of Investigative Dermatology 1998 110, 103-109DOI: (10.1046/j.1523-1747.1998.00107.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions