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

• Published in: Clinical and experimental immunology Vol. 204; no. 1; pp. 49 - 63
• Main Authors: Paradowska‐Gorycka, A., Wajda, A., Stypinska, B., Walczuk, E., Rzeszotarska, E., Walczyk, M., Haladyj, E., Romanowska‐Prochnicka, K., Felis‐Giemza, A., Lewandowska, A., Olesińska, M.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2021; John Wiley and Sons Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers; connective tissue disease; Connective tissue diseases; Endosomes - genetics; Endosomes - metabolism; expression; Female; Gene expression; Gene Expression Profiling - methods; Humans; Interferon; Interferon-alpha - blood; Interferon-alpha - genetics; Interferon-alpha - metabolism; Interferon-beta - blood; Interferon-beta - genetics; Interferon-beta - metabolism; Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interferons - blood; Interferons - genetics; Interferons - metabolism; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - metabolism; Male; Middle Aged; Mixed connective tissue disease; Mixed Connective Tissue Disease - blood; Mixed Connective Tissue Disease - genetics; Mixed Connective Tissue Disease - metabolism; Original; pathogenesis; Scleroderma; Scleroderma, Systemic - blood; Scleroderma, Systemic - genetics; Scleroderma, Systemic - metabolism; Systemic lupus erythematosus; Systemic sclerosis; TLR; Toll-Like Receptor 3 - blood; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; Toll-Like Receptor 7 - blood; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 7 - metabolism; Toll-Like Receptor 8 - blood; Toll-Like Receptor 8 - genetics; Toll-Like Receptor 8 - metabolism; Toll-Like Receptor 9 - blood; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - metabolism; Toll-like receptors; Toll-Like Receptors - blood; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Young Adult; pathogenesis; expression; TLR; interferon; connective tissue disease
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/cei.13566

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. The summary of the article is: “We investigated TLR3/7/8/9 and 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 TLRs‐IFNs expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN‐γ, TLR3, and TLR8 was detected only in SLE patients. Our study indicated that TLRs‐IFNs signaling pathway may be implicated in the pathogenesis of these diseases, but the underlying mechanism is distinct; probably, in each ACTDs, endosomal TLRs are activated on the different cell types and in different immune pathways.