scholarly journals Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jing Xue ◽  
Jiali Yang ◽  
Lijuan Yang ◽  
Shaolan Zhou ◽  
Chen Ji ◽  
...  

An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p<0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p<0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN.

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shuhong Chi ◽  
Yunxia Yu ◽  
Juan Shi ◽  
Yurong Zhang ◽  
Jijuan Yang ◽  
...  

Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated.Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts.Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone.Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease.


Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 241-250 ◽  
Author(s):  
W.A. Wan Asyraf ◽  
M.S. Mohd Shahrir ◽  
W. Asrul ◽  
A.W. Norasyikin ◽  
O. Hanita ◽  
...  

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.


2021 ◽  
Vol 11 (2) ◽  
pp. 97-102
Author(s):  
Saiful Bahar Khan ◽  
Rafi Nazrul Islam ◽  
Md Saif Bin Mizan ◽  
AKM Shahidur Rahman ◽  
Shah Md Zakir Hossain ◽  
...  

Background: Lupus nephritis (LN) is one of the most common and serious manifestations of systemic lupus erythematosus (SLE) that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response in lupus nephritis. This study aimed to compare serum complement levels (C3 and C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with LN after kidney biopsy were included in this study. Serum complement levels (C3 and C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment initiation. These biomarker values before and after treatment were compared between the proliferative and non-proliferative LN patients. Results: Serum C3 levels were significantly different between patients with proliferative LN (Class III and Class IV) and non-proliferative LN (Class V) at baseline (0.47 ± 0.32 g/l versus 0.89 ± 0.43 g/l, p=0.009) and levels changed significantly 6 months after treatment initiation (p<0.001) and likewise for serum C4 levels (0.10 ± 0.06 g/l versus 0.24 ± 0.26 g/l, p=0.040). The values of 24-hr UTP and anti-ds-DNA were significantly different 6 months after treatment with p value <0.05 in both groups but C3 (p<0.001) and renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) (p<0.001) were only significant in the proliferative group. On the other hand, after 6 months treatment, C4 levels became relatively higher but that was not significant in both groups (p>0.05). Conclusion: After 6 months of treatment, serum C3 and C4 levels increased towards normal in both LN groups. Serum C3 and C4 levels in patients with LN correlate with disease activity. Therefore, serum complement (C3 and C4) levels may be utilized as serological biomarkers for treatment response of LN. Birdem Med J 2021; 11(2): 97-102


Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 713-721 ◽  
Author(s):  
Z Adhya ◽  
M El Anbari ◽  
S Anwar ◽  
A Mortimer ◽  
N Marr ◽  
...  

Background Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. Methods A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas’ Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. Results The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. Conclusion These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.


Lupus ◽  
2019 ◽  
Vol 28 (14) ◽  
pp. 1669-1677 ◽  
Author(s):  
R Kandane-Rathnayake ◽  
J R Kent ◽  
W Louthrenoo ◽  
S -F Luo ◽  
Y -JJ Wu ◽  
...  

Objective To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Methods This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Results Patients ( N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Conclusion Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.


2012 ◽  
Vol 5 (1) ◽  
pp. 85 ◽  
Author(s):  
RaghavannairSuresh Kumar ◽  
PankajkumarAshok Kasar ◽  
Milly Mathew ◽  
Georgi Abraham

2014 ◽  
Vol 142 (7-8) ◽  
pp. 431-436 ◽  
Author(s):  
Valentina Zivkovic ◽  
Aleksandra Stankovic ◽  
Tatjana Cvetkovic ◽  
Branka Mitic ◽  
Svetislav Kostic ◽  
...  

Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3?9.7 years on the average, with SLE of average duration 10.37?7.99 years, hospitalized at the Institute ?Niska Banja? during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p<0.01). SLE patients with SLEDAI ?11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p<0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79?83.46 U/ml vs. 57.81?63.15 U/ml; p<0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r=0.443; p<0.001), and anti-C1q antibodies (r=0.382; p<0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r=0.445; p<0.001). Conclusion. Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.


Sign in / Sign up

Export Citation Format

Share Document