Abstract
Background: Pigeon fanciers are at increased risk of Hypersensitivity Pneumonitis (HP), a common interstitial lung disease (ILD). Connective tissue disease (CTD) is also associated with development of ILD, and CTD symptoms are common in pigeon fanciers without CTD. How this links to their risk of ILD is unclear. Single cell RNA sequencing (scRNAseq) can allow unbiased identification of relevant novel pathways.
Objectives: We aimed to map monocyte molecular heterogeneity among pigeon fanciers to test the hypothesis that distinct phenotypes associate with HP/ILD or CTD symptoms.
Methods: Blood monocytes from fanciers categorised as ‘no symptoms’ post pigeon exposure (n=15), previous acute HP/fibrosing ILD (HP/ILD)(n=10), symptoms of CTD (n=12) or ‘post exposure’ symptoms (n=15) were prepared for scRNA-seq. 130,000 cells (500 immune-gene panel) were analysed per subject.
Results: Following agnostic integration (SCTransform algorithm), 5 clusters in classic (CD14hiCD16neg), 3 in non-classic (CD14loCD16hi), and 4 in intermediate (CD14+CD16+) monocytes were identified across all groups. Differences in relative proportions were significant for those with CTD symptoms: an intermediate cluster (dominant gene IFITM2pos) was higher, and a classic cluster (S100A12hi) was lower compared to those without CTD symptoms. Among 15 differentially expressed genes GNAI2 was significantly upregulated (+2.7) in HP/ILD vs CTD.
Conclusions: GNAI2 encodes G-protein Gαi2 which modulates GPCR chemokine receptor responses. Relative expression levels may determine recruitment of selective monocyte clusters to different tissue sites for local pathogenesis or resolution, and may be relevant for the evolution of disease in patients with HP.
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4440.
This article was presented at the 2022 ERS International Congress, in session “-”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022