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

Author:

Paradowska-Gorycka A1ORCID,Wajda A1,Stypinska B1ORCID,Walczuk E1,Rzeszotarska E1,Walczyk M2,Haladyj E3,Romanowska-Prochnicka K24,Felis-Giemza A2,Lewandowska A2,Olesińska M2

Affiliation:

1. Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland

2. Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland

3. Eli Lilly and Company, Indianapolis, Indiana, USA

4. Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland

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.

Funder

Polpharma Scientific Foundation

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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