BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS: Lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.
BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS:Lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.
Authors: Nils Landegren; Norito Ishii; Maribel Aranda-Guillén; Hörður Ingi Gunnarsson; Fabian Sardh; Åsa Hallgren; Mona Ståhle; Eva Hagforsen; Maria Bradley; Per-Henrik D Edqvist; Fredrik Pontén; Outi Mäkitie; Liv Eidsmo; Lars Norlén; Adnane Achour; Ingrid Dahlbom; Ilma Korponay-Szabó; Daniel Agardh; Mohammad Alimohammadi; Daniel Eriksson; Takashi Hashimoto; Olle Kämpe Journal: Proc Natl Acad Sci U S A Date: 2021-12-21 Impact factor: 11.205