Intrarenal and Urinary Th9 and Th22 Cytokine Gene Expression in Lupus Nephritis

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.

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.


2015 ◽  
Vol 10 ◽  
pp. BMI.S27625 ◽  
Author(s):  
Hani Susianti ◽  
Jullyanny W. Wijaya ◽  
Ati Rastini ◽  
Kusworini Handono ◽  
Atma Gunawan ◽  
...  

Background This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity. Methods Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Results The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P > 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r= 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P > 0.05). Conclusion uNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.


Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 560-568 ◽  
Author(s):  
Tatiana N Pedrosa ◽  
Sandra G Pasoto ◽  
Nadia E Aikawa ◽  
Emily FN Yuki ◽  
Eduardo F Borba ◽  
...  

Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar’s test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels.


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.


Lupus ◽  
2021 ◽  
pp. 096120332110305
Author(s):  
Ahmed Fayed ◽  
AbdelAal Mohamed ◽  
Reham Abdelghany Ahmed ◽  
Sameh Abouzeid ◽  
Ahmed Soliman ◽  
...  

Aim Lupus nephritis (LN) is one of the most serious complications of SLE. Tregs (Regulatory T lymphocytes) are thought to play a part in the pathogenesis of SLE. According to recent research, Foxp3, a Treg identification marker, plays a significant role in the pathogenesis of SLE. This study aimed to compare the urinary Foxp3 mRNA levels of patients with active and inactive forms of LN and healthy control subjects to see whether it played a role in disease activity. Methods We measured FOXP3 messenger RNA (mRNA) expression in the urine of 50 people with active LN, 50 people with inactive lupus, and 50 healthy people. Results We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (22.93 ± 4.13 vs 5.66 ± 0.47 vs 0.57 ± 0.15copy; P < 0.001). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (0.000057) In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (< 0.00001). Conclusion We concluded that urinary FOXP3 mRNA is elevated in patients with active LN and that it is linked to the SLEDAI and the severity of the disease. FOXP3 mRNA in urine sediment may be used as a non-invasive biomarker for evaluating the severity of LN and risk stratification.


2020 ◽  
Vol 16 ◽  
Author(s):  
Dina Said ◽  
Nearmeen Mohammed Rashad ◽  
Nora Said Abdelrahmanc ◽  
Ghada Aboelsaud Dawaa

Background:: Lupus nephritis (LN) represents 40%–50% of all systemic lupus erythematosus (SLE) patients, and rapidly progressive glomerulonephritis is associated with significant morbidity and mortality. Antineutrophil cytoplasmic antibody (ANCA) might be involved in the pathogenesis of LN. Objective:: We evaluated the role of myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCA, and anti-glomerular basement membrane autoantibodies (anti-GBM autoAb) for the diagnosis of LN. Methods:: In this cross-sectional study, 95 SLE patients were divided into 2 subgroups: LN group (n = 60) and non-LN group (n = 35). For further analysis, we subclassified the LN group into ANCA-positive (n = 16) and ANCA-negative (n = 44) LN patients. The entire Non-LN group was ANCA-negative. The SLE disease activity index (SLEDAI) was reported for each patient. Determination of MPO-ANCA, PR3-ANCA, and anti-GBM autoAb was performed using a novel multiplex bead-based technology in all patients. Data analyses were done using SPSS, version 20. Approval was obtained from the institutional review board of Zagazig University (ZU-IRB#6000). Results:: Of 95 patients with SLE, 16 patients (16.84%) had ANCA-positive LN, all of which were MPO-ANCA. There was a positive correlation between MPO-ANCA and SLEDAI, as well as with class IV LN. Receiver operating characteristic analyses revealed that the sensitivity and specificity of MPO-ANCA were 81.3% and 99.8%, respectively, in discriminating LN from systemic lupus without nephritis. Conclusion:: MPO-ANCA level was significantly correlated with SLEDAI, inflammatory markers, kidney function tests, and LN class IV.


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.


Author(s):  
Duong Thi Thanh Binh ◽  
Nguyen Thu Huong ◽  
Nguyen Thi Kien ◽  
Pham Van Dem ◽  
Tran Minh Dien

This study describes clinical, paraclinical characteristics and treatment response in children with nephritis class II-IV caused by systemic lupus erythematosus and validates SLEDAI for the evaluation of disease activity and the appropriate treatment strategy. A cross-sectional descriptive study was carried out on 40 children, 37 girls (92%) and 3 boys (8%), with an average age of 11.7 years with lupus nephritis class III- IV in Vietnam National Children’s Hospital in 2019. The study results show that the average score of SLEDAI in the children with pericardial and pleural effusions was 20.94 ± 4.09; high blood pressure, 20.89 ± 4.23; and gross hematuria, 20.29 ± 5.03, which were higher than those in children without these manifestations with p< 0.05. The most common kidney manifestations were nephrotic-range nephritis with renal failure (40%) and Glomerulonephritis (35%), corresponding to an average SLEDAI score of 24.25 ± 5.52 and 24.33 ± 3.2, respectively (p = 0.001). SLEDAI had an inverse correlation with the C3 complement value (r -0.315, p <0.05). The average SLEDAI score decreased gradually from 18.75 ± 4.22 to 3.38 ± 3.95 points (p <0.001) after 12 months of treatment.  The study concludes that SLEDAI score was higher in patients with pleural and/or pericardial effusions, hypertension and gross hematuria, nephrotic-range nephritis with kidney failure or glomerulonephritis. SLEDAI score corresponded with the C3 complement value and the average SLEDAI score decreased gradually with treatment. Keywords: Lupus Nephritis class III- IV, SLEDAI. References [1] George Bertsias, Ricard Cervera và Dimitrios T Boumpas, Systemic Lupus Erythematosus: Pathogenesis and Clinical Features<sample chapter 20_mod 17_Systemic Lupus nephritis 2012.pdf> (2012), EULAR Textbook on Rheumatic Diseases, EULAR, 476-505.[2] D.M. Levy and S. Kamphuis, Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am59(2) (2012)345-64.[3] Thai Thien Nam, 2018, Lupus in National Children,s Hospital, [4] C.Bombardier, M.B. Hurwitz et al, Derivation of the SLEDAI: A disease activity index for lupus patients. The committee on prognosis studies in SLE, Arthritis Rheum 35(6) (1992) 630-640.[5] R. Shamim, S. Farman, S. Batool et al, Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus. Pak J Med Sci. 36(3) (2020) 467-472.[6] Le Thuy Hang, Assesment of SLEDAI score and panthology in children with lupus nephritis, 2016, Pediatrician thesis, Hanoi Medical University.[7] S.K.S.M. Nazri, K.K. Wong and W.Z.W.A. Hamid, Pediatric systemic lupus erythematosus. Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score, Saudi Med J. 39(6) (2018) 627-631. [8] Nguyen Thuy Duong, clinical, paraclinical and pathology characteristics in children with nephritis caused by systemic lupus erythematosus, 2011, Master thesis, Hanoi Medical University.[9] S.N. Wong, W.K. Chan, J.Hui et al, Membranous lupus nephritis in Chinese children--a case series and review of the literature. Pediatr Nephrol, 24(10)(2009) 1989-1996.[10] N.T.N. Dung, H.T. Loan, S. Nielsen et al, Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatric Rheumatology Online Journal, 10 (2010) 38-48.[11] T. Pusongchai, J. Jungthirapanich, S. Khositseth, Pediatric Systemic Lupus Erythematosus in Thammasat University Hospital, J Med Assoc Thai. 93(12) (2010) 283-290.    


2019 ◽  
Author(s):  
Justa Friebus-Kardash ◽  
Marten Trendelenburg ◽  
Ute Eisenberger ◽  
Camillo Ribi ◽  
Carlo Chizzolini ◽  
...  

Abstract Background: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. Methods: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele. Results: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038) (p=0.03 and p=0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p=0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p=0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p=0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p=0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p=0.006; OR, 3.7; 95% CI, 1.27-10.84). Conclusions: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.


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