Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Clin Exp Immunol. 2021 Apr;204(1):49-63. doi: 10.1111/cei.13566. Epub 2021 Jan 17.
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.
我们研究了 Toll 样受体(TLR)-3/-7/-8/-9 和干扰素(IFN)-α/β/γ mRNA 在混合性结缔组织病(MCTD)、系统性红斑狼疮(SLE)和系统性硬皮病(SSc)患者全血和血清 IFN-α/β/γ 水平中的表达,以评估 TLR-IFN 表达与疾病严重程度和易感性之间的关系,并确定潜在的生物标志物。IFN-γ、TLR-3 和 TLR-8 的表达仅在 SLE 患者中检测到。TLR-7、IFN-α 和 IFN-β 的表达在 SLE 中最高,而 TLR-9 的表达在 SSc 患者中最高。在 SLE 和 MCTD 患者中,观察到 TLR-7 与 IFN-α 表达以及 IFN-β 与 IFN-α 表达之间存在强烈相关性。在 MCTD 患者中,发现 IFN-α 与 TLR-9 以及 TLR-7 与 TLR-9 之间呈负相关。抗-U1-70k 阴性、抗-C 阴性和抗-SmB 阴性 MCTD 患者的 TLR-9 表达高于 MCTD 阳性患者。我们观察到 SLE 患者血清 IFN-α 水平与 TLR-7 表达以及 C3 和 C4 水平之间存在负相关。在 SLE 患者中,我们观察到随着 IFN-γ、TLR-3 和 TLR-8 表达的增加,C3 和 C4 的值也增加。我们的结果证实,内体 TLR-IFN 途径在 SLE 中似乎比在 MCTD 或 SSc 中更为重要,IFN-α 和 IFN-β 可能是 SLE 的潜在生物标志物。