Command Palette

Search for a command to run...

Preprint WatchModerateSeptember 25th, 2026

Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease

Tufenkjian TS, Blackburn JB, Nichols D, Vasquez A, Shaver C, Ware L, Blackwell TS, Richmond BW.

Inflammatory cytokines including IL-1 beta drive direct basal-to-goblet cell differentiation in COPD airways through a SERPINB3 and SERPINB4 positive transitional intermediate.

Moderate contradiction

1 prior failure

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

Tufenkjian and colleagues identify a basal-to-goblet transitional cell in COPD airways and report that inflammatory cytokines including IL-1 beta drive that transition through a SERPINB3 and SERPINB4 positive intermediate. The matching entry is canakinumab-il1b-nsclc-canopy1-phase3-efficacy-failure, a Phase 3 efficacy failure of IL-1 beta blockade, which is what raises this to moderate under the severity rule. The indications differ, and that difference is the point. The recorded failure tested IL-1 beta blockade against lung cancer outcomes rather than against airway remodelling, so this preprint does not contradict it. Anyone building an IL-1 beta programme on airway epithelial remodelling should still carry the Phase 3 result forward as evidence about how much clinical change IL-1 beta blockade produced when it was measured at scale.

Abstract excerpt

Goblet cell hyperplasia (GCH) is a hallmark of chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality. We investigated the cellular and molecular origins of GCH in COPD using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and in vitro models. We identified "basal-to-goblet transitional cells" (BGTC) which are transcriptionally and physically located between basal and goblet cells and are characterized by expression of clade B serpins. In vitro studies indicate that inflammatory cytokines, including IL-1β, stimulate basal-to-goblet differentiation through a SERPINB3/4+ intermediate and SERPINB3 overexpression induces differentiation of airway basal cells into IL1B-producing inflammatory goblet cells. In addition, we identified a subset of SERPINB4+ "goblet-variant basal cells" from lungs of COPD patients that express goblet cell and inflammatory genes ex vivo. Together, these results indicate clade B serpins contribute to altered epithelial differentiation and inflammatory signaling in COPD and support therapeutic targeting of clade B serpins to reduce GCH.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.