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Rationale <p>In the INSPIRE trial, patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF) failed to demonstrate improved survival after treatment with IFN-gamma-1β. This outcome became the impetus to develop more personalized approaches to the diagnosis, classification, and management of pulmonary fibrosis.</p> Objective <p>The present study was designed to assess autoantibody profiles in a randomly selected group of INSPIRE trial participants in order to better define IPF on a molecular diagnostic level and define subsets with potentially different underlying disease processes.</p> Methods <p>We performed conventional, gel-based protein and RNA immunoprecipitation (IP) on 483 plasma specimens derived from patients enrolled in both the treatment and placebo arms of INSPIRE. Tandem immunoprecipitation and mass spectrometry proteomics (IP-to-MS) of selected specimens was used to confirm conventional IP interpretation and to identify unknown autoantigens.</p> Results <p>Based on conventional IP approaches, approximately 30% of trial participants had evidence of autoimmune disease-specific autoantibodies and another ~ 10% had evidence of autoantibodies of unknown specificity. IP-to-MS revealed additional autoantigens, including Annexin 11.</p> Conclusions <p>IP analyses demonstrated an unexpectedly high prevalence of autoantibodies potentially indicative of underlying connective tissue disease-associated ILD, underscoring the importance of classification schemes incorporating unbiased autoantibody profiling.</p>

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Revisiting the INSPIRE trial: antibody profiling reveals high prevalence of occult autoimmunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月20日

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  • Marilyn K. Glassberg,
  • Cindy Burg,
  • Simone Pereira-Simon,
  • Benjamin Trzaskoma,
  • Lisa Harlow,
  • Stephanie Biedka,
  • Sharon Elliot,
  • Yingze Zhang,
  • Hannah VanEvery,
  • Noreen Fertig,
  • Jonathan S. Minden,
  • Dana P. Ascherman

摘要

Rationale

In the INSPIRE trial, patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF) failed to demonstrate improved survival after treatment with IFN-gamma-1β. This outcome became the impetus to develop more personalized approaches to the diagnosis, classification, and management of pulmonary fibrosis.

Objective

The present study was designed to assess autoantibody profiles in a randomly selected group of INSPIRE trial participants in order to better define IPF on a molecular diagnostic level and define subsets with potentially different underlying disease processes.

Methods

We performed conventional, gel-based protein and RNA immunoprecipitation (IP) on 483 plasma specimens derived from patients enrolled in both the treatment and placebo arms of INSPIRE. Tandem immunoprecipitation and mass spectrometry proteomics (IP-to-MS) of selected specimens was used to confirm conventional IP interpretation and to identify unknown autoantigens.

Results

Based on conventional IP approaches, approximately 30% of trial participants had evidence of autoimmune disease-specific autoantibodies and another ~ 10% had evidence of autoantibodies of unknown specificity. IP-to-MS revealed additional autoantigens, including Annexin 11.

Conclusions

IP analyses demonstrated an unexpectedly high prevalence of autoantibodies potentially indicative of underlying connective tissue disease-associated ILD, underscoring the importance of classification schemes incorporating unbiased autoantibody profiling.