Stimulation with type I collagen induces changes in gene expression in peripheral blood mononuclear cells from patients with diffuse cutaneous systemic sclerosis (scleroderma)

摘要

An autoantigenic role for collagen type I (CI) has been suggested previously in diffuse cutaneous systemic sclerosis (dcSSc). Whether CI is indeed capable of affecting the immune system in dcSSc is not known. Patients with early (3 years or less) or late (>3 years) dcSSc and healthy controls donated blood. Peripheral blood mononuclear cells (PBMC) were cultured with or without CI, and expression of genes known for their involvement in autoimmune and inflammatory processes was assessed using cDNA arrays; results were confirmed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay for selected genes. Patients with early and late dcSSc were similarly different from healthy controls in basal gene expression. When cultured with CI, PBMC from patients with early dcSSc differed from healthy controls in expression of 34 genes, whereas PBMC from patients with late dcSSc differed from healthy controls in expression of only 29 genes. Direct comparisons of matched PBMC samples cultured with and without CI revealed differences in expression of eight genes in healthy controls, of five genes in patients with early dcSSc, and no differences in patients with late dcSSc. Thus, PBMC from patients with dcSSc respond differently than do PBMC from healthy controls when cultured with CI. Exposure to CI in culture of PBMC from patients in the early stage of dcSSc in contrast to PBMC from patients with late-stage dcSSc evokes a greater degree of activation of immune-related genes, suggesting that CI is more dominant as an autoantigen in early versus late dcSSc.