scholarly journals POS0110 ASSOCIATION OF miR-155 AND miR-34a EXPRESSION IN LUPUS NEPHRITIS RENAL TISSUE WITH DISEASE ONSET AND OUTCOMES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 266.1-266
Author(s):  
C. Di Mario ◽  
L. Petricca ◽  
M. R. Gigante ◽  
S. Costanzi ◽  
G. Vischini ◽  
...  

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In mouse models, different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease1.Objectives:To evaluate the expression of miR-155 and miR-34a in renal tissues as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two SLE patients with LN (age: 32.2 ± 9.2 years) with active renal involvement undergoing ultrasound-guided renal biopsy were enrolled between 2010 and 2019. The nephritic manifestation was present in 13 (41%) patients at disease onset (early-LN SLE), while 19 (59%) patients showed a renal involvement after disease onset (long-LN SLE, mean disease duration at LN onset: 7.3 ± 5.7 years). Twelve age-matched patients with IgA nephropathy were enrolled as control group. Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. MiR-155 and miR-34a expression in renal tissues was carried out by extraction of total RNA from paraffin-preserved biopsies and was evaluated, after a retrotrascription protocol, using real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)2.Results:MiR-155 and miR-34a expression in renal tissues was higher in LN-SLE patients as compared to IgA nephropathy patients (ΔCt miR-155: 9.4 ± 10.1 vs 21.9 ± 3.6, p<0.01; ΔCt miR-34a: 10.1 ± 9.8 vs 19.2 ± 3.1, p=0.02). MiR-155 and miR-34a expression in LN-SLE patients renal tissues was comparable in the different histological classes. Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p <0.001). Dividing patients based on nephritic onset, SLE patients with long-LN showed higher expression of miR-155 (ΔCt 6.1 ± 8.7) and miR-34a (ΔCt 7.1 ± 9.0) as compared to patients with early-LN (miR-155: ΔCt 13.4 ± 10.6 p = 0.08; miR-34a: ΔCt 15.1 ± 9.5 p = 0.02) or patients with IgA nephropathy (miR-155 p<0.01 and miR-34a p<0.01). Moreover, in early-LN SLE it was observed an inverse correlation between miR-34a expression and C3 and C4 complement components (r=-0.7.2; p=0.05 and r=-0.86; p=0.01, respectively) and a direct correlation between miR-155 and 24h-UP (r=0,67; p=0.03). Considering SLE patients with early-LN, the expression of miR-34a was slightly significant in patients who had relapsed (ΔCt 8.2 ± 11.4 vs ΔCt 18.4 ± 7.9 p = 0.08), although no correlation emerged between the expression of miR-155 and miR-34a at the time of the biopsy and with disease activity indices.Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in SLE patients with LN; in particular, the higher expression of these miRNA in long-LN and the correlation between miR-155 expression with p24h-UP in early-LN could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of patients.References:[1]Leiss H et al. Plosone 2017.[2]Alivernini S et al. Nat Commun 2018.Disclosure of Interests:None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 889.2-890
Author(s):  
C. DI Mario ◽  
L. Petricca ◽  
G. Vischini ◽  
A. Paglionico ◽  
S. Alivernini ◽  
...  

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In particular, in mouse model (1), different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease.Objectives:The aim of the study was to evaluate the expression of miR-155 and miR-34a in renal tissue as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two LN patients with active renal involvement were enrolled (age: 32.2 ± 9.2 years). The nephritic onset of the disease (early-SLE) was present in 13 patients (41%), while 19 patients (59%) showed a renal involvement during the follow-up (long-SLE). Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. Ultrasound-guided renal biopsy has been performed for each patients for the definition of the nephritic class according to the ISN / RPS classification of 2003 revised in 2018(2). The expression of miR-155 and miR-34a in renal tissue was carried out by extraction of total RNA from paraffin-preserved biopsies and after a retrotrascription protocol was evaluated using SYBR® Green-based real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)(3).Results:Mir-155 and miR-34a expression in renal tissue were comparable in the different histological classes. Dividing patients on the base of nephritic onset, patients with early SLE showed lower expression of miR-155 (ΔCt 12.8 ± 10.8) and miR-34a (ΔCt 14.6 ± 9.9) than patients with long-SLE (miR-155: ΔCt 6.1 ± 8.7 p = 0.02; miR-34a: ΔCt 7.1 ± 9.0 p = 0.03). Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p <0.001). Considering patients with early-SLE, the expression of miR-34a was slightly significant in patients who had relapsed (ΔCt 8.2 ± 11.4 vs ΔCt 18.4 ± 7.9 p = 0.08), although no correlation emerged between the expression of miR-155 and miR-34a both at the time of the biopsy and with the disease activity indices. At the histological evaluation, miR-155 and miR-34a were more expressed in Early-SLE patients who had wire loop lesions (miR-155: ΔCt 19.5 ± 7.7 vs ΔCt 7.3 ± 9.6 p = 0.05; miR-34a: ΔCt 21,7 ± 1.1 vs ΔCt 8,8 ± 9.7 p= 0.05) possibly associated with a greater activation of the inflammatory component.Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in patients with LN in particular the higher expression of these miRNA in Long-SLE patients could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of the patient.References:[1] Leiss H et al. Plosone 2017[2] Bajema IM et al Kidney Int. 2018[3] Alivernini S et al. Nat Commun 2018Disclosure of Interests:None declared


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.


2018 ◽  
Vol 12 (1) ◽  
pp. 129-138 ◽  
Author(s):  
Lisandra Torres Hartmann ◽  
Ana Paula Alegretti ◽  
Alice Beatriz Mombach Pinheiro Machado ◽  
Eduardo Ferreira Martins ◽  
Rafael Mendonça da Silva Chakr ◽  
...  

Introduction: The Mean Platelet Volume (MPV) is a platelet activation biomarker that has been recently correlated with disease activity in SLE. We aimed to evaluate the MPV in patients with SLE comparing it with healthy individuals, to study the correlation between MPV and SLE Disease Activity Index (SLEDAI) in SLE patients and to analyze possible correlation between MPV and Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), and complement components C3 and C4. Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Active disease was defined as SLEDAI>0. Results: Patients with active SLE had decreased MPV when compared to inactive disease group (10.0±0.7fL vs. 10.7±1.0fL, p=0.005, respectively) and when compared to control group (10.9±1.0fL, p<0.001). Our study found a weak negative correlation between the SLEDAI and the MPV (r=-0.29, p=0.009). There was no correlation between MPV and CRP, ESR, C3 and C4. Also, no correlation between SLEDAI and CRP, ESR, C3 and C4 was found. Conclusion: MPV decreases in patients with active SLE and is inversely correlated with SLEDAI.


2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Sahar A. Elsayed ◽  
Omar M M. Mohafez

Abstract Background Specific autoantibodies are considered as an important marker in autoimmune rheumatic diseases and are of great value for the diagnosis and prognosis of systemic lupus erythematosus (SLE) patients. A total of eighteen autoantibodies were analyzed for their positivity in SLE patients and we evaluated the clinical relevance of the five most frequent autoantibodies: anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro60, and anti-Ro52 on disease activity and renal affection in SLE Egyptian patients. Results Immunological profile and correlation of the five autoantibodies with disease activity and histopathological pattern of renal involvement were analyzed for 190 SLE patients. Lupus nephritis (LN) patients showed much worse constitutional and mucocutaneous manifestations than patients without nephritis. Autoantibody profile showed a significant increased frequency of anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro-60, and anti-Ro52 antibodies in LN patients. The impact of the co-positivity of the autoantibodies on the renal function was obvious. Moreover, the disease activity increased by the increased frequency of autoantibodies positivity in LN patients. ROC curve analysis showed that anti-nucleosome had the highest sensitivity; 93% followed by anti-dsDNA 83.3% then anti-histone 73.8%, but anti-Ro60 and anti-Ro52 showed a humble sensitivity. Furthermore, the highest frequency of positivity for the five autoantibodies was found in class-III and class-IV LN patients. Conclusion Detection of anti-dsDNA, anti-nucleosome, anti-histone, and anti-Ro60 in SLE patients may be important for predicting disease progression and kidney affection. Moreover, anti-nucleosome and anti-dsDNA show high sensitivity and specificity for lupus nephritis, thus patients with four to five positive autoantibody panels should be kept under close monitoring as they may warrant considering aggressive therapy to control their disease and prevent renal damage.


2021 ◽  
Author(s):  
Doron Rimar ◽  
Merav Lidar ◽  
Nasrin Eiza ◽  
Adi D Sabag ◽  
Elias Toubi ◽  
...  

Abstract Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Jia ◽  
Lingling Zhao ◽  
Chunyan Wang ◽  
Jin Shang ◽  
Yi Miao ◽  
...  

Objectives. We aimed to evaluate the value of immunoglobulin (Ig) G, IgM, and IgA isotypes of anti-double-stranded DNA (anti-dsDNA) and anti-C1q antibody in diagnosing systemic lupus erythematosus (SLE) patients and elucidate their association with disease activity and lupus nephritis. Methods. Blood samples were obtained from 96 SLE patients, 62 other autoimmune disease patients, and 60 healthy blood donors. Anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody were measured by enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to the SLE Disease Activity Index score. Results. When specificity was greater than 90%, the sensitivity of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody in diagnosing SLE was 75%, 45%, 33%, and 49%, respectively. The prevalence of anti-dsDNA IgG (p=0.002), anti-dsDNA IgA (p=0.028), and anti-C1q antibody (p=0.000) in active cases was significantly higher than those in inactive ones. In addition, the presence of anti-C1q antibody was associated with renal involvement (p=0.032). Anti-dsDNA IgM showed no significant association with disease activity, but it was inversely linked with lupus nephritis (p=0.005). When anti-dsDNA IgG and IgA and anti-C1q were combined to evaluate SLE disease activity, the specificity reached the highest level (90%). When anti-C1q positive was accompanied by anti-dsDNA IgM negative, the specificity of diagnosing lupus nephritis was up to 96%. Conclusions. This study demonstrated the role of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody alone or combination in diagnosing SLE. Anti-dsDNA IgG and IgA and anti-C1q were shown to be associated with disease activity, while anti-dsDNA IgM and anti-C1q were associated with lupus nephritis. When the related antibodies were combined, the diagnostic specificity was significantly higher.


2020 ◽  
Vol 11 ◽  
Author(s):  
Nellie Bourse Chalvon ◽  
Pauline Orquevaux ◽  
Delphine Giusti ◽  
Gregory Gatouillat ◽  
Thierry Tabary ◽  
...  

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer &gt;6 U/ml).ResultsThe cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (&gt;10 U/ml) by the automated technique, three sera were found “ambivalent” (&gt;7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.


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.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher Sjӧwall ◽  
Chelsea Bentow ◽  
Mary Ann Aure ◽  
Michael Mahler

Objective. Anti-double-stranded (ds) DNA and anti-C1q autoantibodies are useful tools in the assessment of disease activity and nephritis in systemic lupus erythematosus (SLE) patients. This study aimed to explore the utility of these antibodies along with anti-Ku antibodies in an oligoparametric model approach for the assessment of disease activity and lupus nephritis. Methods. Samples from 261 well-characterized SLE patients were tested using chemiluminescent immunoassays (CIA) for anti-dsDNA and anti-Ku antibodies as well as by anti-C1q antibody ELISA (Inova Diagnostics, USA). Of these SLE patients, 26.4% had lupus nephritis (LN) at the time of blood draw or had a history of LN, and modified SLE disease activity index-2K (SLEDAI) scores were used to assess disease activity. Results. All three antibodies demonstrated higher prevalence and higher antibody levels in active versus inactive SLE patients and in LN versus non-LN patients. When oligoparametric analysis was performed, the likelihood of LN and patients with active disease increased with dual and triple positivity. Conclusions. Anti-dsDNA and anti-C1q antibodies are useful tools to identify disease activity and/or renal involvement in SLE patients. In addition, the combination of those antibodies in a two-parametric score might improve the clinical utility of those markers.


2019 ◽  
Vol 8 (2) ◽  
pp. 133-139
Author(s):  
Mohammad Reza Jafari Nakhjavani ◽  
Sima Abediazar ◽  
Amir Ghorbanihaghjo ◽  
Behnaz Hanafizadeh ◽  
Sepideh Zununi Vahed ◽  
...  

Introduction: The neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a biomarker of renal damage. Objectives: The aim of this study was to assess the serum levels of NGAL (sNGAL) as a marker of disease activity in individuals with lupus nephritis (LN). Patients and Methods: This study contained 50 systemic lupus erythematosus (SLE) individuals with (n = 25) and without (n = 25) nephritis, and 39 healthy controls. The sNGAL levels were measured by ELISA. Renal function test, urinary parameters, lupus serology activity, and also calculated SLE disease activity index (SLEDAI) were analyzed to determine their associations with sNGAL. Results: The results revealed that the SLE individuals with or without nephritis had a raised serum NGAL levels as compared to control subjects (P<0.001). Additionally, sNGAL levels in LN individuals were meaningfully higher compared to those in non-LN patients (P<0.001). Serum NGAL showed a significant correlation with the SLEDAI, serum creatinine, and 24-h urinary protein (P<0.05). More importantly, sNGAL had a significant positive correlation with the activity index of LN (r = 0.616, P=0.001). In the ROC curve analysis, the measurement of sNGAL level showed a good diagnostic performance for distinguishing individuals with LN from SLE patients without renal involvement with AUC=0.902 (P<0.001), 72% sensitivity, and 99% specificity. Moreover, sNGAL could identify all of SLE patients from controls with high accuracy, AUC= 0.99, P<0.001, with 99% sensitivity, and 97% specificity. Conclusion: Serum NGAL had an association with clinical parameters and could discriminate LN from SLE patients without renal involvement. Our result suggests that serum NGAL can be used for early diagnosis of LN and identifying active LN.


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