Persistent and progressive acute lung allograft dysfunction is linked to cell compositional and transcriptional changes in small airways

Summary

Recipients with undifferentiated acute lung allograft dysfunction (ALAD) and stable controls had small airway brushings analysed by single-cell RNA sequencing. Groups were control (n=8) and ALAD with recovered (n=4), persistent (n=5) or progressive (n=3) FEV1 decline, across 68,140 cells. Cell composition was linked to ALAD outcome (PERMANOVA p=0.004); worse outcomes correlated with loss of basal cells, changes in club and ciliated subsets, loss of macrophages and expansion of cytotoxic T cells. The previously published AI2 gene score rose with worse outcome, and pathway analysis showed increased interferon signalling. The authors call it a pilot study. The groups are very small.

Details

doi

10.1016/j.healun.2025.03.010

pmid

40293382

authors

Brunet-Ratnasingham E, Yellamilli S, Guo R, Mohanty RP, Duong A, Kolaitis NA, Hays SR, Shah RJ, Venado A, Maheshwari JA, Kleinhenz ME, Leard LE, McDyer J, Martinu T, Combes AJ, Calabrese DR, Singer JP, Greenland JR

journal

The Journal of Heart and Lung Transplantation

year

2025

volume

44

issue

9

pages

1482-1492

Sources and links

• Publisher record via DOI (primary)
• PubMed 40293382

Related

Links from this record

• studies: Acute lung allograft dysfunction (ALAD)
• evidence for: Airway transcriptomic signatures
• describes: Cytotoxic and senescent T cells
• authors affiliated with: Toronto Lung Transplant Program (University Health Network)
• coauthor: Tereza Martinu

Linked from (derived)

• author affiliation matches this institution (OpenAlex): UCSF Lung Transplant Program
• author: Tereza Martinu
• evidence: Definitions and prognosis of ALAD and BLAD are not settled
• evidence: Human tissue studies are small and raw human sequence data are often not open

Known gaps in this record

• full text not read (abstract only)
• funding statement and grant numbers
• whether the data are deposited publicly