Variety of endosomal TLRs and Interferons (IFN-α, IFN-β, IFN-γ) expression profiles in patients with SLE, SSc and MCTD

Abstract

Summary We investigated Toll‐like receptor (TLR)‐3/‐7/‐8/‐9 and interferon (IFN)‐α/β/γ mRNA expression in whole blood and serum IFN‐α/β/γ levels in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and in healthy subjects to assess the association between the TLR–IFN expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN‐γ, TLR‐3 and TLR‐8 was detected only in SLE patients. TLR‐7, IFN‐α and IFN‐β expression was highest in SLE, while TLR‐9 expression was highest in SSc patients. In SLE and MCTD patients a strong correlation was observed between TLR‐7 and IFN‐α expression and IFN‐β and IFN‐α expression. In MCTD patients, negative correlation between IFN‐α and TLR‐9 and TLR‐7 and TLR‐9 was revealed. TLR‐9 expression in anti‐U1‐70k‐negative, anti‐C negative and anti‐SmB‐negative MCTD patients was higher than in MCTD‐positive patients. We observed negative correlations between serum IFN‐α levels and TLR‐7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN‐γ, TLR‐3 and TLR‐8 expression increased the value of C3 and C4. Our results confirmed that the endosomal TLR–IFN pathway seems to be more important in SLE than in MCTD or SSc, and that IFN‐α and IFN‐β may be possible biomarkers for SLE.

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

“…IFN- γ has been secreted mainly by CD4 T helper cells, CD8 cytotoxic T cells, and to a less extent by antigen-presenting cells (APCs) and natural killer cells [ 32 ]. The peripheral blood mononuclear cells (PBMCs) of SLE patients showed high level of IFN- γ transcript, and the T cells of SLE patients produce much more IFN- γ as compared to normal cells [ 33 ]. In the current study, strong interactions of three peptides (i.e., DEDTQAMMPFR, QEPQESQQ, and FRDEHKK) were found with the active amino acids present in the binding pocket of IFN- γ which could be used as potential inhibitors of IFN- γ to treat SLE.…”

Reduced expression of hematopoietic progenitor kinase 1 in T follicular helper cells causes autoimmunity of systemic lupus erythematosus

“…4,5 The Tfh cells have been proved to play an important role in the pathogenesis of SLE, with a significantly increased proportion in the peripheral blood circulation of patients with SLE. The expressions of IL-21 6 , BAFF, 7 IFNγ, 8 and IL-17A 9 are significantly higher in SLE patients than that in normal controls. IL-21 is the main cytokine for Tfh cells to execute effector functions and promote the differentiation and maturation of B cells, generation of plasma cells, production and class conversion of immunoglobulin.…”

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

“…High IFN-activity associate with SLE disease activity as observed in European and North American cohorts [ 5 , 16 , 20 ]. A certain auto-antibody profile has been coupled with high IFN-activity, including anti-dsDNA, anti-RNP, anti-Sm and anti-Ro autoAbs, rather than the antiphospholipid antibody profile (aPL) [ 20 , 21 , 22 ]. In our Karolinska SLE cohort high functional IFN-activity correlate positively with disease activity scores (both SLEDAI and SLAM) and, also with certain organ active involvement: e.g., nephritis, arthritis, lymphadenopathy, fatigue and weight loss [ 5 ].…”

“…The majority of information on the role of IFN-β in SLE comes from gene expression studies, where signatures of IFN-β and IFN-αs partially overlap [ 15 , 22 ]. Data indicate that levels of IFN-β and IFN-α overlap [ 21 ]. Detailed knowledge on which SLE manifestations or phenotypes, if any, are associated with high circulating IFN-β levels remain to be studied.…”