Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway

Abstract

The results indicate that the type I IFN pathway is activated in patient subsets of five rheumatic diseases and suggest that these subsets may benefit from anti-IFN therapy.

Gene Expression Profiling in Rheumatoid Arthritis

“…This cluster contains highly correlated genes such as IFRG28 (28 kDa interferon-responsive protein), IFI35 (interferoninduced protein 35), IFI44L (interferon-induced protein 44-like), IFIT1 (interferon-induced protein with tetratricopeptide repeats 1), IFIT2, IRF2 (interferon-regulatory factor 2), IRF7, GIP2 (interferon a-inducible protein 2), GIP3, SERPING1 (serine proteinase inhibitor clade G member 1, C1 inhibitor), OAS1 (29-59-oligoadenylate synthetase 1), OAS2, MX1 (Myxovirus resistance 1), ISG15 (interferon-induced protein 15) and RSAD2 (radical S-adenosyl methionine domain containing 2). These findings have now been replicated in several other studies using independent cohorts (Thurlings et al, 2010;O'Hanlon et al, 2011;Higgs et al, 2011;Vosslamber et al, 2011). Moreover, IFN-bioactivity was measured in RA serum.…”

Type I IFNs Regulate Inflammation, Vasculopathy, and Fibrosis in Chronic Cutaneous Graft-versus-Host Disease

“…More recently, we have reported that treatment of patients with SLE with a neutralizing anti-IFN-a mAb reduces cutaneous inflammation and the expression of a number of key inflammatory genes in patients (29). Similarly, a peripheral IFN "gene signature" has also been described in patients with scleroderma (30), although the role of type I IFNs in the pathogenesis of this disease is at present unknown. To further understand the contribution of type I IFNs in scleroderma, we used a model of chronic immune GVHD (31) that mimics many aspects of SSc, including overexpression of type I IFN-inducible genes in skin.…”

FcγRIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulates Toll-like Receptor (TLR) Expression

“…IFN-␥ influences chromatin remodeling and enhance accumulation of follicular helper T-cells (T FH ) population during the formation of ectoid lymphoid follicles (23,24). The IFN-inducible gene signature is observed in rheumatoid arthritis (RA) and SLE and serves as a marker for disease severity in SLE (25)(26)(27).…”