Elevation of serum soluble tumour necrosis factor receptors in patients with polymyositis and dermatomyositis

Abstract

The aim of the study was, to examine the relationship between serum levels of soluble tumour necrosis factor receptors (sTNF-R) and the gene expression of two types of receptor for TNF (TNF-R), a 55 a receptor (TNF-R1) and a 75 kDa receptor (TNF-R2), bloodin peripheral mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). Soluble tumour necrosis factor receptor 1 (sTNF-R1) and soluble tumour necrosis factor receptor 2 (sTNF-R2) levels in sera from patients were measured by enzyme-linked immunosorbent assay. Expression of TNF-R1 and TNF-R2 mRNAs in PBMC was analysed by Northern blotting. Serum sTNF-R1 and sTNF-R2 levels were elevated significantly in 25 patients with active-stage PM/DM, compared to those in 18 patients with inactive-stage PM/DM and 32 normal controls. Serum concentrations of sTNF-R1 and sTNF-R2 were correlated with PM/DM disease activity. TNF-R1 gene expression was enhanced in freshly isolated PBMC from patients with active-stage PM/DM. In contrast, TNF-R2 mRNA was expressed constitutively in patients with active-stage PM/DM and in normal controls. The expression of TNF-R1 and TNF-R2 mRNAs in PBMC and elevation of their soluble forms in the sera of patients with active-stage PM/DM suggest increased proteolytic cleavage of cell surface TNF-R from PBMC in patients with active-stage PM/DM, and that sTNF-R may regulate TNF-alpha-mediated muscle fibre damage in PM/DM.