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Background <p>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.</p> Methods <p>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).</p> Results <p>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.</p> Conclusions <p>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.</p>

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Autoantibody repertoire analysis in paraneoplastic pemphigus reveals novel targets linked to mucocutaneous blistering and bronchiolitis obliterans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月10日

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  • Daniel Eriksson,
  • Maribel Aranda-Guillén,
  • Norito Ishii,
  • Axel Cederholm,
  • Anish Behere,
  • Fahad Ahmed,
  • Juliaana Katto,
  • Sara Öster,
  • Helen Kaipe,
  • Dhifaf Sarhan,
  • Olle Kämpe,
  • Takashi Hashimoto,
  • Nils Landegren

摘要

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.