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.
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.
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].
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).
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.
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.
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.
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.
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).
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.
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.
Moreover, the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1β, IL-18, and NLRP3 in the muscle (for IL-1β, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs. control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P= 0.0017, PM vs. control, P= 0.0006).
The messenger RNA of cytokines is variably expressed, except for a persistent up-regulation of interleukin 1beta in inclusion body myositis and transforming growth factor beta in dermatomyositis.
Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity.
Muscle biopsy tissues from 10 patients with polymyositis or dermatomyositis and 7 healthy control subjects were investigated by immunohistochemistry using antibodies against IL-1 receptor type I (IL-1RI), IL-1RII, IL-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1Ra).
Muscle biopsy tissues from 10 patients with polymyositis or dermatomyositis and 7 healthy control subjects were investigated by immunohistochemistry using antibodies against IL-1 receptor type I (IL-1RI), IL-1RII, IL-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1Ra).
This case demonstrates that typical muscle lesions of dermatomyositis can occur in the presence of a complement defect which would preclude activation of the classic (C1-C4-C2) complement pathway.
Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population.