Background: COPD is a heterogeneous disease involving different lung compartments. Changes in extracellular matrix (ECM) components, including basement membrane (BM) proteins, are associated with the disease progression. The alteration in collagen IV (colIV), a major component of the BM, and the precise distribution of six distinct colIV ?-chains remains relatively understudied. Therefore, spatial expression and distribution of ECM proteins such as, colIV could help with phenotypic stratification of COPD patients

Aim: To identify differential expression and distribution of diverse ColIV chains in different lung compartments of COPD patients

Methods: We performed multiplex immunofluorescence (mIF) for compartmental profiling of six type IV collagen ?-chains combined with cell-type specific markers and analyzed publicly available single cell RNA sequencing (scRNA-seq) profiles (GSE136831) from donor and COPD lungs

Results: mIF showed differential geographic distribution of six colIV ?-chains in various compartments of donor lungs. This abundance was different as compared with COPD lungs. Similarly, RNAseq analysis revealed different cell-type specific enrichment patterns of ?-chains. The alveolar region was enriched in colIV ?2,a3 and a4 chains whereas the bronchiolar region of donor and COPD lungs was enriched in ?2,3,4,5 and 6 chains. In the vascular EC region, the expression of colIV ?1 and 2 chains was prominent. A significant difference in the expression of ?3,a4,a5 and a6 chains was observed between donor and COPD lungs

Conclusion:We identified a divergent ColIV ?-chain expression signature between donor and COPD lung, which could be used in the future to define different COPD phenotypes