New cellular clues to complications of scleroderma

A Northwestern Medicine research study identified cellular mechanisms behind complications faced by individuals with systemic sclerosis, or scleroderma. This rare autoimmune disease impacts skin and internal organs, with gastrointestinal involvement being common, causing severe acid reflux, swallowing issues, and impaired esophageal motility.

By analyzing over 306,000 cells from esophageal tissue samples, the research team discovered that patients with scleroderma experienced a reduction in mature cells in the outermost layer of the esophagus, compared to healthy individuals. The majority of gene expression changes occurred within these remaining cells, with increased production of extracellular matrix and keratinization genes.

These findings suggest that chronic acid reflux, rather than alterations in the esophageal lining itself, drives the majority of epithelial abnormalities in systemic sclerosis. The researchers also observed that these reflux-related changes were more pronounced in the upper esophagus of scleroderma patients, potentially explaining the disease's effects beyond the digestive tract.

While the epithelial changes were largely driven by reflux, the study also revealed unique biological signals specific to systemic sclerosis, including dysregulation of immunoregulatory pathways and increased communication between fibroblasts and smooth muscle cells. This latter finding may contribute to impaired esophageal motility.

The study's findings could support personalized treatment approaches for systemic sclerosis and highlight the need to explore deeper tissues beyond the epithelium for a more comprehensive understanding of the disease. The research utilized single-cell and spatial transcriptomic technologies to provide a detailed view of cellular changes in the esophagus of patients with systemic sclerosis.