Trial reportRespiratory research2026
Revisiting the INSPIRE trial: antibody profiling reveals high prevalence of occult autoimmunity.
Trial report in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
12 authors.
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Abstract
rationaleIn 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.
objectiveThe 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.
methodsWe 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.
resultsBased 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.
conclusionsIP 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.
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