Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up

Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1800-1806
Author(s):  
Sujata Ganguly ◽  
Sanjukta Majumder ◽  
Sandeep Kumar ◽  
Ranjan Gupta ◽  
Hafis Muhammed ◽  
...  

Introduction Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. Methods Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. Results Twenty eight AN of median age of 26.5 (20–31.50) years and disease duration of 3 (0.7–5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98–1296) ng/mg which fell significantly to 62.69 (28.04–502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5–46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00–1550.43) µg/ml to 338.52 (211.35–525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. Conclusion Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.

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.


2017 ◽  
Vol 131 (8) ◽  
pp. 653-671 ◽  
Author(s):  
Kwok Fan Cheung ◽  
Susan Yung ◽  
Mel K.M. Chau ◽  
Desmond Y.H. Yap ◽  
Kwok Wah Chan ◽  
...  

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance.


2015 ◽  
Vol 42 (7) ◽  
pp. 1150-1155 ◽  
Author(s):  
Cathy Choi-Wan Luk ◽  
Lai-Shan Tam ◽  
Bonnie Ching-Ha Kwan ◽  
Priscilla Ching-Han Wong ◽  
Terry King-Wing Ma ◽  
...  

Objective.We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE).Methods.We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects.Results.There was no detectable IL-9 mRNA in all samples. Patients with proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels than those with nonproliferative nephritis (2.2 ± 5.4 vs 8.6 ± 20.0 copies, p = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological activity index (r = −0.427, p < 0.0001). In contrast, patients with lupus nephritis had significantly higher urinary IL-10 mRNA levels than patients with HTN (7.8 ± 18.5 vs 1.9 ± 4.0 copies, p = 0.012), and urinary IL-10 mRNA levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was significantly lower among patients who achieved complete remission than those with partial remission or no response (4.1 ± 6.5 vs 14.1 ± 28.0 copies, p = 0.036).Conclusion.Urinary IL-22 mRNA level is decreased in patients with SLE with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also predict treatment response. These results suggest that urinary mRNA levels of IL-10 and IL-22 might be used as biomarkers for assessing disease activity and risk stratification in lupus nephritis.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael A. Smith ◽  
Jill Henault ◽  
Jodi L. Karnell ◽  
Melissa L. Parker ◽  
Jeffrey M. Riggs ◽  
...  

Abstract Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.


2012 ◽  
Vol 39 (10) ◽  
pp. 1948-1954 ◽  
Author(s):  
RENATA FERREIRA ROSA ◽  
KIOKO TAKEI ◽  
NAFICE C. ARAÚJO ◽  
SÔNIA M.A. LODUCA ◽  
JOSÉ C.M. SZAJUBOK ◽  
...  

Objective.Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA.Methods.Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA.Results.In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%.Conclusion.The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice.


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.


2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Mervat E. Abdelazeem ◽  
Marwa I. Abdelhaleem ◽  
Rabab A. Mohamed ◽  
Enas A. Abdelaleem

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1059.1-1060
Author(s):  
S. Soliman ◽  
A. Haque ◽  
S. Mason ◽  
L. Greenbaum ◽  
M. J. Hicks ◽  
...  

Background:Proteomic screening is an efficient approach for identifying protein biomarkers in various inflammatory diseases. Our preliminary proteomic analysis revealed elevated levels of serum Axl, Ferritin, IGFBP4 and sTNFR2 in adult patients with active lupus nephritis (LN) (1). However, the role of these serum biomarkers in pediatric systemic lupus erythematosus (SLE) patients has not been examined.Objectives:To evaluate the performance of 4 serum protein markers for detecting disease activity in pediatric patients with SLE.Methods:83 pediatric patients who fulfilled ≥4 ACR criteria for SLE and 25 healthy controls were recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using the SLEDAI-2k score, renal disease activity was assessed by the renal SLEDAI (range 0-16; 0= inactive LN, ≥ 8= active renal). 57 patients had clinically active SLE (SLEDAI score ≥ 4 or having a flare) (28 active renal and 29 active non-renal SLE patients). In active renal patients, concurrent renal biopsy was performed, unless contraindicated. The ISN/RPS criteria were used to assess the histopathologic features of LN. Those Patients were further subcategorized into 2 groups; active proliferative (ISN/RPS classes III/IV) and non-proliferative (classes I/II/V).Results:The serum concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE (3765±235 vs. 2513±130 pg/ml,P= 0.001) and (111±26 vs. 18±4 ng/ml,P =0.0001) respectively. Serum Axl levels were significantly higher in active renal versus active non-renal SLE patients (3765±235.3 vs. 2825±200.7 pg/ml,P= 0.04). In the active renal patients with paired kidney tissue and blood samples, none of the biomarkers tested discriminated classes of LN, although serum Axl, ferritin and IGBPB4 levels were higher in the proliferative subgroup. The levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores (Axl, r= 0.58,P<0.0001; ferritin, r= 0.53,P<0.0001; IGFBP4, r= 0.229,P= 0.03). However, only serum Axl levels correlated significantly with the renal SLEDAI (r= 0.46,P= 0.01). The levels of Axl, IFGBP4 and sTNFR2 correlated with decreased C3 levels (r= - 0.54,P<0.0001; r= - 0.29,P= 0.007; r= - 0.29,P= 0.007) respectively. Only serum Axl and ferritin correlated with urinary PCR (r= 0.42,P<0.0001; r= 0.22,P=0.04) respectively. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA or decreased C3. The specificity values of serum ferritin and IGFBP4 for concurrent active lupus nephritis were higher than anti-dsDNA or C3. Serum ferritin was the best predictor of global SLE activity (AUC 0.81,P<0.0001), followed by C3 (AUC 0.79,P<0.0001) then Axl (AUC 0.71,P= 0.002), while both Axl and C3 were the best predictors of lupus nephritis activity (AUC 0.72, both).Conclusion:In pediatric SLE patients, serum ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these serum markers should be explored further in a longitudinal cohort of pediatric SLE patients.References:[1]Wu T, Ding H, Han J, et al. Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study. J Proteome Res. 2016 Jul 1;15 (7): 2102-14.Disclosure of Interests:None declared


Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 311-323 ◽  
Author(s):  
N Bona ◽  
E Pezzarini ◽  
B Balbi ◽  
S M Daniele ◽  
M F Rossi ◽  
...  

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and β2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers ( P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.


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