4.5 Article

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

Journal

CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 204, Issue 1, Pages 49-63

Publisher

OXFORD UNIV PRESS
DOI: 10.1111/cei.13566

Keywords

connective tissue disease; expression; interferon; pathogenesis; TLR

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Funding

  1. Polpharma Scientific Foundation

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Our investigation found that IFN-gamma, TLR-3, and TLR-8 expression were present in SLE patients, while expression levels were relatively low in MCTD and SSc patients. Strong correlations were observed between TLR-7 and IFN-alpha expression, as well as between IFN-beta and IFN-alpha expression in SLE and MCTD patients. The endosomal TLR-IFN pathway appears to be more significant in SLE compared to MCTD or SSc, suggesting IFN-alpha and IFN-beta may serve as potential biomarkers for SLE.
We investigated Toll-like receptor (TLR)-3/-7/-8/-9 and interferon (IFN)-alpha/beta/gamma mRNA expression in whole blood and serum IFN-alpha/beta/gamma 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-gamma, TLR-3 and TLR-8 was detected only in SLE patients. TLR-7, IFN-alpha and IFN-beta 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-alpha expression and IFN-beta and IFN-alpha expression. In MCTD patients, negative correlation between IFN-alpha 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-alpha levels and TLR-7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN-gamma, 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-alpha and IFN-beta may be possible biomarkers for SLE.

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