Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis

Lupus ◽  
2022 ◽  
pp. 096120332110671
Author(s):  
Rasha F Ahmed ◽  
Olfat Gamil Shaker ◽  
Hend M abdelghany ◽  
Nilly Helmy Abdallah ◽  
Samar Hisham Elsayed ◽  
...  

Background The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. Purpose The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. Research Design This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. Results SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001). Conclusion miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

Lupus ◽  
2016 ◽  
Vol 25 (14) ◽  
pp. 1602-1609 ◽  
Author(s):  
C Lourdudoss ◽  
A-C Elkan ◽  
I Hafström ◽  
T Jogestrand ◽  
T Gustafsson ◽  
...  

Objective The aim of this study was to investigate the role of dietary micronutrient intake in systemic lupus erythematosus (SLE). Methods This study included 111 SLE patients and 118 age and gender-matched controls. Data on diet (food frequency questionnaires) were linked with data on Systemic Lupus Activity Measure, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and carotid atherosclerotic/echolucent plaque (B-mode ultrasound). Dietary micronutrient intake were compared between SLE patients and controls and in relation to lupus activity and atherosclerosis in SLE. Associations between micronutrient intake and plaque were analyzed through logistic regression, adjusted for potential confounders. Results Micronutrient intake did not differ between patients and controls, and between lower and higher lupus activity, apart from the fact that phosphorus was associated with SLEDAI > 6. In SLE patients, some micronutrients were associated with atherosclerotic plaque, left side. Lower intake of riboflavin and phosphorus was associated with atherosclerotic plaque, left side (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.12–8.40 and OR 4.36, 95% CI 1.53–12.39, respectively). Higher intake of selenium and thiamin was inversely associated with atherosclerotic plaque, left side (OR 0.28, 95% CI 0.09–0.89 and OR 0.26, 95% CI 0.08–0.80, respectively). In addition, higher intake of thiamin was inversely associated with echolucent plaque, left side (OR 0.22, 95% CI 0.06–0.84). Lower intake of folate was inversely associated with bilateral echolucent plaque (OR 0.36, 95% CI 0.13–0.99). Conclusions SLE patients did not have different dietary micronutrient intake compared to controls. Phosphorus was associated with lupus activity. Riboflavin, phosphorus, selenium and thiamin were inversely associated with atherosclerotic plaque, left side in SLE patients, but not in controls. Dietary micronutrients may play a role in atherosclerosis in SLE.


Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2161-2165 ◽  
Author(s):  
J Barbado ◽  
S Tabera ◽  
A Sánchez ◽  
J García-Sancho

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50–90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.


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.


2021 ◽  
Vol 7 ◽  
Author(s):  
Malarvili Selvaraja ◽  
Voon Kin Chin ◽  
Maha Abdullah ◽  
Masita Arip ◽  
Syafinaz Amin-Nordin

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.


2019 ◽  
Vol 22 ◽  
pp. 365-375
Author(s):  
Tianbiao Zhou ◽  
Xialan Zhang ◽  
Wenshan Lin ◽  
Shujun Lin

Introduction: We evaluated the effectiveness and safety of various multitarget therapies for inducing remission in lupus nephritis patients. Methods: Randomized controlled trials (RCT) were identified and extracted from the Embase, PubMed, Chinese Biomedical Literature Database (CBM), and the Cochrane Library until Oct 31, 2018, investigations meeting inclusion criteria were extracted, and data were analyzed by meta-analysis. The total remission (TR; complete to partial remission), complete remission (CR), albumin, proteinuria levels, negative rate of anti-double-stranded DNA antibody (ds-DNA), negative rate of anti-nuclear antibody (ANA), and systemic lupus erythematosus disease activity index (SLE-DAI) were calculated using the software of RevMan 5.3. Results: Eleven RCTs were included and analyzed. The multitarget therapy group exhibited a higher value of CR (OR=3.06, 95%CI: 2.35-3.99, P﹤0.00001) as well as TR (OR=3.83, 95%CI: 2.77-5.31, P﹤0.00001) than those in the cyclophosphamide (CYC) group. In addition, multitarget therapies had more albumin (WMD=3.50, 95%CI: 1.04-5.95, P=0.005), greater albumin increases (OR=1.96, 95%CI: 0.63-3.29, P=0.004) and higher negative rates of ds-DNA (OR=2.13, 95%CI: 1.51-3.01, P﹤0.0001) and ANA (OR=2.82, 95%CI: 1.77-4.50, P﹤0.0001) when compared with the CYC group. This group also had less proteinuria levels (WMD=-0.55, 95%CI: -0.79 to -0.30, P﹤0.0001), lower degrees of SLE-DAI (OR=-1.80, 95%CI:-2.78 to -0.81, P=0.0004), and a lower adverse reaction rate. For example, gastrointestinal syndrome, irregular menstruation and leucopenia happened less frequently in the multitarget therapy group. However, hypertension was more prevalent in the multitarget therapy group. Conclusions: Multitarget therapy is an effective and safe intervention for inducing remission in lupus nephritis patients.


Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 607-616
Author(s):  
Asmaa SM Abdel-Rehim ◽  
Nesrine A Mohamed ◽  
Marwa M Shakweer

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.


Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1549-1557 ◽  
Author(s):  
L P Whittall-García ◽  
J Torres-Ruiz ◽  
A Zentella-Dehesa ◽  
M Tapia-Rodríguez ◽  
J Alcocer-Varela ◽  
...  

Objective This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. Methods Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. Results In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs ( r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score ( r = 0.514, p = 0.001), anti-dsDNA antibodies ( r = 0.467, p = 0.004), the rate of glomerular filtration descent ( r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index ( r = 0.581, p = 0.004), fibrinoid necrosis ( r = 0.603, p = 0.002), and cellular crescents ( r = 0.486, p = 0.019). Conclusions In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.


Lupus ◽  
2021 ◽  
pp. 096120332110614
Author(s):  
Valeria Erazo-Martínez ◽  
Ivana Nieto-Aristizábal ◽  
Isabella Ojeda ◽  
Michelle González ◽  
Cristian C Aragon ◽  
...  

Objective Pregnant women with SLE have higher probabilities of maternal complications. SLE during pregnancy has alternating patterns of remission and flare-ups; however, most pregnant SLE patients tend to worsen with associated poor obstetric and perinatal outcomes. This study aimed to describe obstetric outcomes in pregnant women with SLE. Methods This retrospective study was performed between 2011 and 2020 at a highly complex referral health center in Cali, Colombia. Pregnant women with a diagnosis of SLE were included. Demographic, clinical, and laboratory features and obstetric and fetal outcomes, including intensive care unit (ICU) characteristics, were evaluated. Results Forty-eight pregnant women with SLE were included. The median age was 29 (25–33.7) years. The SLE diagnosis was made before pregnancy in 38 (79.1%) patients, with a median disease duration of 46 (12–84) months. Thirteen (27.1%) patients had lupus nephritis. Preterm labor (34, 70.8%), preeclampsia (25, 52%), and preterm rupture of membranes (10, 20.8%) were the most common obstetric complications. A relationship between a greater systemic lupus erythematosus pregnancy disease activity index (SLEPDAI) and the development of hypertensive disorders during pregnancy was established (preeclampsia = p < 0.0366; eclampsia = p < 0.0153). A relationship was identified between lupus nephritis (LN) and eclampsia ( p < 0.01), preterm labor ( p < 0.045), and placental abruption ( p < 0.01). Seventeen (35.4%) patients required ICU admission; 52.9% of them were due to AID activity, 17.6% for cardiovascular damage, 11.7% for septic shock, and 5.8% for acute kidney failure. Fetal survival was 89.5% ( N = 43/48). Among the live births, two (4.2%) newborns were diagnosed with neonatal lupus, and two (4.2%) were diagnosed with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage. Conclusions This study is the first to describe SLE during pregnancy in Colombia. SLE was the most prevalent AID in this cohort, and complications included preterm labor, preeclampsia, and postpartum hemorrhage. A higher SLEPDAI and lupus nephritis predicted adverse maternal outcomes.


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.


2021 ◽  
Vol 8 (1) ◽  
pp. e000458
Author(s):  
Huijing Wang ◽  
Yunjie Gao ◽  
Yanhong Ma ◽  
Fanghao Cai ◽  
Xiaohan Huang ◽  
...  

ObjectiveTo evaluate the performance of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis (LN) and their renal prognosis.MethodsPatients with newly diagnosed SLE attending and followed up for >12 months were included. A retrospective review of all patients with renal biopsy fulfilling a consensus expert opinion during 2014 and 2018. Clinical, serological and pathological data were collected and each patient was assigned a high/low criteria scores (HS/LS) group. Survival curves for flare adjusted for multiplicity on renal flares, was applied to the two groups.ResultsApplying EULAR/ACR criteria in our cohort of 126 patients, 6 (4.76%) did not meet the criterion, resulting in a sensitivity of 95.24%. The EULAR/ACR criteria scores was positively correlated with SLE disease activity index scores. Additionally, we noticed that a significant difference in clinical and immunological manifestations between HS and LS group. We observed a higher proportions of class Ⅲ or Ⅳ LN and lower proportions of class Ⅱ or V LN (p=0.034) and pathological higher activity index in HS group (p=0.007). Compared with LS groups, patients involved more severe renal damage and achieved higher rate of complete remission in the HS group. The Kaplan-Meier exploratory analyses, adjusted for LN classification, estimated glomerular filtration rate, activity index and chronicity index and induction and maintenance treatments, showed that patients in the HS group had a tendency of higher renal flare risk than that in the LS group (HR=0.21, p=0.04).ConclusionsThe EULAR/ACR criteria performed high sensitivity in identifying SLE in this cohort of biopsy-confirmed LN. Patients with LN with high criteria scores had more extrarenal manifestations, and worse renal prognosis in the short and long terms.


Sign in / Sign up

Export Citation Format

Share Document