The TLRs and IFNs in patients with connective tissue diseases

Abstract

Autoimmune connective tissue diseases (ACTD) are characterized by spontaneous stimulation of the immune system and the production of autoantibodies. Some autoantibodies may create an immune complex with DNA and/or RNA and promote tissue inflammation. Immune complexes that contain nucleic acids can act as ligands for endosomal Toll-like receptors (TLR), which activation induces secretion of the type I and type III interferons. The present study aimed to determine whether TLRs and IFNs genes could be considered as potential ACTD biomarkers. IFN-A and IFN-G showed a relationship with a predisposition to the development of SLE and MCTD, and IFN-B with a predisposition to the development of SLE. The TLR7 rs5743305 T allele and rs5743316 A allele may play a protective role against the development of MCTD, and the TLR7 rs1731479 T allele and TLR8 rs17256081 C allele may be predictors of MCTD development. mRNA expression of the IFN-α, IFN-β, IFN-γ, TLR3, TLR8 and TLR7 was significantly higher in patients with SLE compared to patients with MCTD and SSc. MCTD patients with anti-U1-70k (+) had higher IFN-γ and lower IFN-β serum levels than patients without this antibody. In patients with SLE, serum levels of IFN-α and IFN-γ correlate with the concentration of complement components, and serum levels of IFN-α with disease activity. The study confirmed that the TLR-IFN pathway may be considered as an important pathogenic mechanism for ACTD.