Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM).
Stratification by ethnicity indicated the TNF-α-308A allele polymorphism was found to be significantly associated with DM in Europeans (OR = 1.977, 95% CI 1.413-2.765, P<0.0001).
The haplotype analysis revealed a significant association between TNF -1031C/-863C/-857C/-308G/+489G haplotype with both DM (P = 0.022) and SLE (P = 0.007) in women.
The expression levels of TLR2, TLR4, TLR9, IFNgamma, IL4, IL17, and TNFalpha were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNgamma, IL4, IL17, and TNFalpha.
The TNF-308A allele demonstrated a strong association with each myositis disease subgroup vs controls [PM, odds ratio (OR) 2.8, 95% confidence interval 1.9-4.3; DM, OR 2.5, 1.6-3.8; CTD-overlap, OR 3.3, 2.1-5.1].
In 65 patients with poly- or dermatomyositis the inflammatory cytokine balance was evaluated by the assessing absolute levels as well as the ratio between TNF and IL-10 in serum.
These findings have prompted some investigators to use off-label, TNF-inhibitors in DM/PM patients, especially if they had failed corticosteroids, immune gamma-globulin, and traditional immunosuppressive agents.
HLA-DRB1 and TNF promoter genotypes were determined, and serum antinuclear autoantibodies were identified in 120 adult Japanese patients with IIM [72 with dermatomyositis (DM), 30 with polymyositis (PM), 18 with myositis overlapping with other collagen vascular diseases], as well as in 265 controls.
HLA-DRB1 studies in a large homogenous cohort of UK Caucasian patients have confirmed that polymyositis (PM) and dermatomyositis (DM) are not genetically identical diseases while other studies have shown that tumor necrosis factor alpha is genetically implicated in disease susceptibility.
We previously found an association of the overproducing TNFalpha-308 A variant with adult dermatomyositis and with subacute cutaneous lupus erythematosus.
In polymyositis (PM)/dermatomyositis (DM), various cytokines, especially macrophage-derived cytokines such as IL-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha, are expressed in the inflammatory foci.
TNF-alpha was more highly expressed in PM and DM than was previously thought, and it was suggested that TNF-alpha plays a role in muscle fiber degeneration in PM.