BACKGROUND: To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. METHODS: Toll-like receptor family (TLR 1-10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. RESULTS: TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. CONCLUSION: Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nefritida při lupus erythematodes * genetika krev MeSH
- systémový lupus erythematodes krev genetika MeSH
- toll-like receptory * genetika biosyntéza MeSH
- vaskulitida centrálního nervového systému při lupus erythematodes * krev genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and serum as a marker of neuronal damage may be a potential biomarker of neuropsychiatric involvement in SLE (NPSLE). METHODS: 80 patients with SLE were included.We obtained paired serum and CSF samples from 48 patients (NPSLE n=32, non-NPSLE n=16) and 31 controls. The serum and CSF levels of NfL were determined using ELISA. RESULTS: Patients with NPSLE demonstrated significantly higher levels of serum NfL compared with the non-NPSLE group (mean 31.68±36.63 pg/mL vs mean 16.75±12.48 pg/mL, respectively, p<0.05) and with controls (mean 10.74±4.36 pg/mL, p<0.01). Notably, CSF NfL concentrations in patients with NPSLE showed an upward trend (mean 1600±2852 pg/mL) in contrast to non-NPSLE patients (mean 393.4±191.9 pg/mL) and controls (mean 509.7±358.5 pg/mL). Furthermore, a positive correlation was observed between serum and CSF NfL levels in patients with NPSLE (R=0.8686, p<0.01). Elevated serum triacylglycerol concentrations, C reactive protein and organ damage were linked to increased serum (p=0.002; p<0.001; p=0.036) and CSF (p=0.008; p=0.007; p<0.001) NfL concentrations. In addition, we established a significant correlation between intrathecal NfL concentrations and interleukin-6 levels in the CSF of patients with NPSLE (R=0.5118, p<0.05). CONCLUSION: The serum NfL levels may be a readily available marker of neuropsychiatric involvement in SLE.
- MeSH
- biologické markery * krev mozkomíšní mok MeSH
- dospělí MeSH
- ELISA MeSH
- interleukin-6 krev mozkomíšní mok MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- neurofilamentové proteiny * krev mozkomíšní mok MeSH
- průřezové studie MeSH
- studie případů a kontrol MeSH
- vaskulitida centrálního nervového systému při lupus erythematodes * krev mozkomíšní mok MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this study was to determine the role of the tumor necrosis factor like weak inducer of apoptosis (TWEAK) as a serum biomarker of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE). Levels of TWEAK levels were measured in sera of 92 patients with systemic lupus erythematosus (SLE), including 28 patients with neuropsychiatric lupus, and in 59 healthy controls using ELISA. All SLE patients underwent rheumatological, neurological and psychiatric assessment. We found no significant differences in TWEAK levels, between SLE patients and the healthy controls (p=0.2411). Similarly, no difference was observed between subgroup of NPSLE and healthy controls (p=0.7658). The mean SLE disease activity (SLEDAI) was 13.25. No correlations between TWEAK levels with disease activity (SLEDAI, r=0.2113, p=0.2805) or the most common NPSLE manifestations such as headache (r=0.2079), seizures (r=0.1101), cerebrovascular disease (r= 0.2347), cognitive dysfunction (r=0.1597) and anxiety (r=0.1397) were observed. Our data do not support the use of serum TWEAK as a discriminating biomarker for NPSLE. The role of the TWEAK in NPSLE remains to be investigated.
- MeSH
- biologické markery krev MeSH
- cytokin TWEAK krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- úzkost krev diagnóza psychologie MeSH
- vaskulitida centrálního nervového systému při lupus erythematodes krev diagnóza psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH