Spatial transcriptomic profiling reveals fibroblast and inflammatory signatures in calcinosis of chronic cutaneous lupus.

Calcinosis cutis represents a debilitating complication of chronic cutaneous lupus erythematosus; however, its underlying molecular mechanisms remain poorly understood. We performed spatial transcriptomic profiling on skin biopsies from 4 patients with chronic cutaneous lupus erythematosus: 2 with calcinosis cutis and 2 without. Analysis of 87,730 cells across 6 major cell types revealed distinct molecular signatures associated with calcification. Fibroblasts in calcinosis cutis lesions exhibited significant upregulation of osteogenic and extracellular matrix genes, including periostin, collagen family members, and matrix metalloproteinase 2, accompanied by enrichment of pathways related to extracellular matrix organization and ossification. Endothelial cells demonstrated activation of hypoxia-responsive pathways, particularly hypoxia-inducible factor 2-alpha. Macrophages showed elevated chemokine receptor expression with corresponding ligand upregulation in endothelial cells, establishing a potential chemotactic recruitment axis. Spatial analysis revealed that these pathological features were concentrated in pericalcinosis regions, with reduced intercellular distances between functionally related cell populations. These findings demonstrate coordinated fibroblast osteogenic reprogramming, endothelial hypoxic responses, and immune cell activation within organized pericalcinosis niches. This spatial transcriptomic characterization of lupus-associated calcinosis cutis identifies potential therapeutic targets and reveals mechanisms resembling those in other calcifying disorders.

Abstract from PubMed