Spatial transcriptomic profiling of the lung tissues from a patient with recurrent anti-synthetase syndrome associated interstitial lung disease after bilateral lung transplantation and one untreated patient

Background: A 58-year-old male with anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD) underwent bilateral lung transplantation (LTx) but experienced ILD progression and myositis worsening 38 weeks post-transplant, despite glucocorticoids, tacrolimus, and mycophenolic acid treatment. High-dose glucocorticoids led to adverse effects and ILD exacerbation upon tapering.Objective: To identify persistent inflammatory pathways despite anti-rejection therapy.Methods: 10X Visium HD spatial transcriptomic analysis was conducted on lung tissues from two distinct patients: one untreated patient with ASS-ILD without LTx serving as a control, and another patient who experienced bilateral LTx. This analysis aims to investigate the inflammatory profiles within the lung tissues and to explore the correlation between pulmonary lesions and systemic inflammation.Results: In comparison to the control patient, the lung tissue from the post-transplant patient appeared to have an increased proportion of macrophages, with a concurrent decrease in the proportions of plasma cells and T cells. Among the macrophages of interest, the post-transplant patient appeared to have an elevated proportion of alveolar macrophages, whereas the control patient seemed to have a larger proportion of monocyte-derived macrophages. Considering that interstitial pneumonia is often driven by alveolar epithelial cell injury, we observed that the post-transplant patient appeared to have a higher proportion of transitional AT2 cells, which were appeared to express both AT2-specific markers (SFTPC, SFTPD) and AT1-specific markers (AGER, RTKN2, GPRC5A).Conclusions: We presented a complicated case of a patient with early recurrence of underlying ASS-ILD after bilateral LTx. We used spatial transcriptomic analysis to investigate the differences between systemic inflammatory responses and lung tissue responses.