Communications medicine · 2026
Autoantibody repertoire analysis in paraneoplastic pemphigus reveals novel targets linked to mucocutaneous blistering and bronchiolitis obliterans.
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Eriksson Daniel, Aranda-Guillén Maribel, Ishii Norito, Cederholm Axel, Behere Anish, Ahmed Fahad, Katto Juliaana, Öster Sara, Kaipe Helen, Sarhan Dhifaf, Kämpe Olle, Hashimoto Takashi, Landegren Nils
Аннотация
BACKGROUND: Paraneoplastic autoimmunity develops as consequences of immune reactions to cancer and exhibits a wide range of clinical manifestations. The autoimmune signs are often visible before the underlying malignancy is diagnosed, and a prompt diagnosis of paraneoplasia is crucial to enable early tumor detection. We characterized the immune responses underlying the severe mucocutaneous blistering disease paraneoplastic pemphigus.
METHODS: We used a two-step approach to proteome-wide autoantibody repertoire analysis and independent validation in patients with paraneoplastic pemphigus (n = 84) and non-paraneoplastic autoimmune blistering diseases (n = 103).
RESULTS: Our findings reveal that paraneoplastic pemphigus features a broad repertoire of disease-specific autoantibodies that mainly target tissue-specific proteins in the skin and mucous membranes. Importantly, we identify SERPINB3 as a major autoantibody target with an expression pattern and clinical association suggesting a role in bronchiolitis obliterans. Autoantibody profiles are similar across neoplasias, except in thymoma patients, who additionally express multiple cytokine autoantibodies.
CONCLUSIONS: Our findings reveal a disease-defining autoantibody repertoire in paraneoplastic pemphigus that corresponds with clinical manifestations and holds high potential for early cancer detection in patients with blistering disease.
METHODS: We used a two-step approach to proteome-wide autoantibody repertoire analysis and independent validation in patients with paraneoplastic pemphigus (n = 84) and non-paraneoplastic autoimmune blistering diseases (n = 103).
RESULTS: Our findings reveal that paraneoplastic pemphigus features a broad repertoire of disease-specific autoantibodies that mainly target tissue-specific proteins in the skin and mucous membranes. Importantly, we identify SERPINB3 as a major autoantibody target with an expression pattern and clinical association suggesting a role in bronchiolitis obliterans. Autoantibody profiles are similar across neoplasias, except in thymoma patients, who additionally express multiple cytokine autoantibodies.
CONCLUSIONS: Our findings reveal a disease-defining autoantibody repertoire in paraneoplastic pemphigus that corresponds with clinical manifestations and holds high potential for early cancer detection in patients with blistering disease.