Biomarker For Lupus Nephritis Research Articles

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family.

Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240pg/ml cutoff point (AUC 0.809). For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN.

Small RNAs encoded by human endogenous retrovirus K overexpressed in PBMCs may contribute to the diagnosis and evaluation of systemic lupus erythematosus as novel biomarkers.

This study aimed to identify the genes and small RNAs (sRNAs) expressed by the human endogenous retrovirus K (HERV-K) HML2 and their associations with the immune process of systemic lupus erythematosus (SLE). RNA-Seq data including 99 SLE patients and 18 controls (GSE72420) was obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) as well as HML2-DEGs between SLE patients and normal controls were identified. Five HML2-DEGs involved in immune-regulating function were identified using weighted gene co-expression network analysis. The associations between these genes and the proportions of immune cells were determined by CIBERSORT. Ten candidate HML2-encoded sRNAs were identified based on specific criteria, and three of them were further validated in SLE patients by qRT-PCR. The diagnostic values of these three sRNAs were evaluated in SLE and lupus nephritis (LN). This study suggested that HML2 genes and their encoded sRNAs might be involved in the immune regulation and progress of SLE. These potential sRNAs might function as regulatory molecules and diagnostic biomarkers of SLE and LN.

Identification and Validation of IFI44 as Key Biomarker in Lupus Nephritis.

Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE) and is a major cause of SLE related deaths. Early diagnosis is essential to improve the prognosis of patients with LN. To screen the potential biomarkers associated with LN, we downloaded the gene expression profile of GSE99967 from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was utilized to construct a gene co-expression network and identify gene modules associated with LN. Gene Ontology (GO) analysis was also applied to explore the biological function of genes and identify the key module. Differentially expressed genes (DEGs) were identified and Maximal Clique Centrality (MCC) values were calculated to screen hub genes. Furthermore, we selected promising biomarkers for real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) validation in independent cohorts. Our results indicated that five hub genes, including IFI44, IFIT3, HERC5, RSAD2, and DDX60 play vital roles in the pathogenesis of LN. Importantly, IFI44 may considered as a key biomarker in LN for its diagnostic capabilities, which is also a promising therapeutic target in the future.

Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review

Introduction: While renal biopsy remains the gold standard for diagnosing lupus nephritis (LN), the prognostic and diagnostic role of non-invasive biomarkers for LN is currently debated. Methods: Available studies published in last 5 years (2015–2020) assessing the diagnostic and prognostic value of urinary and/or serological biomarkers in subjects with LN were analyzed in this systematic review. Results: Eighty-five studies were included (comprehending 13,496 patients with systemic lupus erythematosus [SLE], 8,872 LN, 487 pediatric LN, 3,977 SLE but no LN, 160 pediatric SLE but no LN and 7,679 controls). Most of the studies were cross-sectional (62; 73%), while 14 (17%) were prospective. In sixty studies (71%), the diagnosis of LN was biopsy-confirmed. Forty-four out of 85 (52%) investigated only serological biomarkers, 29 studies (34%) tested their population only with urinary biomarkers, and 12 (14%) investigated the presence of both. Outcome measures to assess the clinical utility of the analyzed biomarkers were heterogeneous, including up to 21 different activity scores, with the SLEDAI (in 60%) being the most used. Despite some heterogeneity, promising results have been shown for biomarkers such as urinary monocyte chemoattractant protein, urinary adiponectin, and urinary vascular cell adhesion protein 1. Discussion/Conclusion: While serum and urine biomarkers have the potential to improve diagnostic and prognostic pathways in patients with LN, the vast heterogeneity across studies severely limits their applicability in current clinical practice. With the kidney biopsy still representing the gold standard, future efforts should focus on harmonizing study inclusion criteria and outcomes, particularly in clinical trials, in order to improve comparability and facilitate the implementations of available biomarkers into the daily practice.

Evaluation of urinary FOXP3 mRNA as a biomarker of lupus nephritis in Egyptian patients with systemic lupus erythematosus.

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. 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. 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). 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.

Evaluation of urinary podocyte level as a noninvasive biomarker in lupus nephritis

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominately affects women. It is characterized by a broad spectrum of immunologic and clinical manifestations. Lupus nephritis (LN) is documented as one of the most severe complication of SLE. Aim To investigate the intensity of podocyturia in LN as a noninvasive biomarker and its relation to grade of disease activity. Patients and methods This is a case–control study. It was carried out on 60 patients and 20 control. All participants were randomly selected from those admitted in the internal medicine and rheumatology departments in Al Zahraa University Hospital, Al Hussein University Hospital, and Sayed Galal University Hospital in the period from March 2019 to March 2020. These patients were divided into three groups: group I included 20 healthy controls, group II included 20 patients SLE without nephritis, and group III included 40 patients with LN, which was subdivided into IIIA, which included 20 highly active LN cases and IIIB, which included 20 inactive LN cases. Results In the current work, there was a highly statistically significant difference among the studied groups regarding hemoglobin, white blood cells, creatinine, urea, albumin/creatinine ratio, estimated glomerular filtration rate, anti-DNA, C3, C4, erythrocyte sedimentation rate, C-reactive protein, and antinuclear antibody. Moreover, there was a highly significant difference among the studied groups regarding urinary podocyte marker. There was a statistically significant positive correlation between podocyte marker and creatinine, urea, albumin/creatinine ratio, and anti-DNA in all patients. There was a positive correlation between immunoglobulin (Ig) Cγ and urea and between Ig Cκ and albumin/creatinine and a negative correlation between Ig Cκ and C4 in group III A (active LN). Conclusion SLE deleteriously affects the fine glomerular structures as reflected by augmented urinary levels of podocyte, so we suggested urinary podocyte as a highly sensitive, early, and noninvasive biomarker of LN.

Serum complement levels as prognostic marker for monitoring treatment response in lupus nephritis

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.&#x0D; 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.&#x0D; 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&lt;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 &lt;0.05 in both groups but C3 (p&lt;0.001) and renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) (p&lt;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&gt;0.05).&#x0D; 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.&#x0D; Birdem Med J 2021; 11(2): 97-102

MiR-384 is associated with renal damage in lupus nephritis via regulation of TET3 expression

Purpose: To investigate the correlations between miR-384 expression and renal damage in lupus nephritis (LN).Methods: Lupus nephritis and normal tissues were collected during surgery. The relative miR-384 expression was evaluated by extracting RNA and performing quantitative real time PCR (qRT-PCR) assays. Expression of ten-eleven translocation (TET3) mRNA and protein were measured by qRT-PCR and western blotting, respectively. The 24-h urine protein, serum complement C3, and serum creatinine were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. TargetScan and luciferase assays were used to validate the binding site for miR-384 and its target mRNA. Relationships among miR-384, TET3, and renal damage were analyzed by Spearman rank-order correlation coefficients.Results: MiR-384 expression increased in LN tissues and was positively correlated with the activity index (AI) and chronicity index of LN, whereas miR-384 expression and serum complement C3 were negatively correlated. Positive correlations were observed between miR-384 expression and 24-h urine protein, serum creatinine, and systemic lupus erythematosus disease AI. TargetScan and luciferaseassays indicated that the TET3 3′-UTR was the direct target of miR-384. MiR-384 upregulation inhibited TET3 mRNA and protein expression, and was negatively associated with renal damage in LN.Conclusion: MiR-384 upregulation contributes to renal damage in LN by targeting the 3′-UTR of TET3 mRNA, suggesting that miR-384 is a potential biomarker and therapeutic target in LN.&#x0D; Keywords: MiR-384, Renal damage, Lupus nephritis, Ten-eleven translocation, TET3

Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model.

Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.

Basophils as a potential marker of lupus nephritis by flow cytometry.

Objective:To establish a convenient and simple flow cytometry immunophenotyping panel to explore immune cellular alterations and potential cellular biomarkers in systemic lupus erythematosus.Materials and methods:This is a cross-sectional, case–control study including 60 patients with systemic lupus erythematosus and 20 sex- and age-matched healthy controls. A 14-color immunophenotyping panel was applied to detect proportions of circulating immune mononuclear cells, and comparisons between patients and healthy controls, and subgroups of patients, were performed. Correlations between cellular proportions and other parameters were investigated.Results:After multivariate analysis, significantly decreased proportions of CD4−CD8− T cells, natural killer cells and innate lymphoid cells were observed in patients compared with healthy controls. The proportions of basophils were decreased significantly in patients with lupus nephritis (LN) compared with those in patients without LN.Conclusion:In the present study, we found that basophil proportions may be a biomarker of LN.

Novel Biomarkers for Lupus Nephritis in the "OMICS" Era.

Lupus nephritis (LN) is severe renal comorbidity associated with systemic lupus erythematosus (SLE), a complex autoimmune disorder with high morbidity and mortality. Diagnosis and monitoring of LN patients still rely on renal biopsy, a procedure that exposes patients to a variety of risks and is not capable of providing longitudinally information about disease prognosis. In this review, we summarized current data of recent promising biomarkers developed in the precision medicine era, particularly under genomic, transcriptomic, proteomic, and metabolomic techniques. Genome-wide association studies have been evaluating the role of endogenous elements beyond the autoimmunity in LN. Transcriptomic methods, including single-cell sequencing, are potential tools in identifying inflammatory signatures, miRNAs, and gene expression. Proteomic measures, including anti-C1q antibodies, cytokines, TLRs, VCAM-1, NGAL osteopontin, angiostatin, have been considered helpful to provide a more profound comprehension of the disease pathogenic processes. Metabolomic approaches may identify several abnormal metabolite profiles related to the impairment of cellular functions. Together, these accurate, non-invasive, and moderate-cost propedeutic resources may be the novel tools for recognizing, distinguishing, and predicting LN progression and prognosis. Furthermore, omics evaluation may also predict responsiveness to treatment and, consequently, change the way we manage LN cases in the near future.

Diagnostic value of TWEAK for predicting active lupus nephritis in patients with systemic lupus erythematosus: a systematic review and meta-analysis

Purpose Accumulative studies showed that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) was up-regulated in the blood and urine from patients diagnosed with lupus nephritis (LN) and that it might be used as a novel biomarker for active LN. This meta-analysis aimed to determine the diagnostic value of TWEAK in active LN. Methods We searched the Cochrane Library, Embase, PubMed, Springer, Wanfang and CNKI databases for articles published up to 20 August 2020. The diagnostic capacity of TWEAK for active LN was assessed using pooled sensitivity and specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). Quality assessment and publication bias were also evaluated. STATA 11.0 and Meta-Disc 1.4 were used to perform these analyses. Results Nine cross-sectional studies were included in this meta-analysis. The overall pooled sensitivity of TWEAK for the diagnosis of active LN was 0.69 (95% CI, 0.63–0.75), and specificity was 0.77 (95% CI, 0.71–0.82). The overall pooled PLR and NLR were 3.31 (95% CI, 2.05–5.35) and 0.38 (95% CI, 0.26–0.55), respectively, with a DOR of 10.89 (95% CI, 6.73–17.63) and AUC (SE) of 0.8276 (0.0289). Deeks’ funnel plot revealed that the publication bias was insignificant in the study (p = .32). Conclusions Our results suggest that TWEAK might be a potential biomarker for patients with active LN. Future cross-sectional and longitudinal studies are needed to confirm its diagnostic value, as well as to establish more definite cutoff for active LN.

Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis

IntroductionVascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in lupus nephritis (LN) and can be easily assessed in urine. The aim of this study was to assess urinary soluble VCAM-1 (uVCAM-1) as a biomarker of disease activity and treatment response in LN.MethodsThis prospective study enrolled 62 patients with class III, IV or V LN diagnosed within the last 3 years and divided them in two groups: with and without active nephritis at the inclusion, each group with 31 patients. At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was assessed.ResultsMedian uVCAM-1 level was elevated in patients with active compared to inactive LN (P < 0.001). The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and specificity (74.2%) for the diagnosis of active LN. A significant correlation was found between uVCAM-1 level and renal activity scores and traditional biomarkers of LN. The level of uVCAM-1 dropped in patients with active LN who went into remission (P < 0.001), increased in patients who went into activity (P = 0.002) and did not change in patients who remained inactive (P = 0.797). The level of uVCAM-1 peaked during the flare of LN (P < 0.05).ConclusionThe uVCAM-1 is a reliable biomarker that reflects renal disease activity and is useful for monitoring individual patients with lupus nephritis over time.

Lupus Nephritis: Role of Serum Complement Levels as Prognostic Marker

Background: Lupus Nephritis (LN) is one of the most common and serious manifestations in Systemic Lupus Erythematosus (SLE) patients that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response of lupus nephritis. Objective: To compare serum complement levels (C3 &amp; 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 lupus nephritis after kidney biopsy were included in this study. Serum complement levels (C3 &amp; 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. These biomarker values before and after treatment were compared between the treatment response and non response groups. Results: Serum C3 levels were significantly different in patients of proliferative lupus nephritis (Class III &amp; Class IV) than non proliferative lupus nephritis (Class V) at baseline (0.47 ± 0.32 vs0.89 ± 0.43g/l, p = 0.009) and levels changed significantly 6 months after treatment (p &lt;0.001) and likewise for Serum C4 levels (0.10 ± 0.06 vs0.24 ± 0.26g/l, p = 0.040). Serum C3 levels were also found to correlate significantly with SLEDAI and renal SLEDAI. No significant difference was observed for 24-hr UTP levels at baseline between remission and non-remission groups. Conclusion: Serum C3 &amp; C4 levels may be utilized as serological biomarkers to predict and monitor the treatment response of lupus nephritis.

Targeted urine proteomics in lupus nephritis – a meta-analysis

ABSTRACT Background Proteomic approaches are central in biomarker discovery. While mass-spectrometry-based techniques are widely used, novel targeted proteomic platforms have enabled the high-throughput detection of low-abundance proteins in an affinity-based manner. Urine has gained growing attention as an ideal biofluid for monitoring renal disease including lupus nephritis (LN). Methods Pubmed was screened for targeted proteomic studies of LN urine interrogating ≥1000 proteins. Data from the primary studies were combined and a meta-analysis was performed. Shared proteins elevated in active LN across studies were identified, and relevant pathways were elucidated using ingenuity pathway and gene ontology analysis. Urine proteomic data was cross-referenced against renal single-cell RNAseq data from LN kidneys. Results Two high-throughput targeted proteomic platforms with capacity to interrogate ≥1000 proteins have been used to investigate LN urine. Twenty-three urine proteins were significantly elevated in both studies, including 10 chemokines, and proteins implicated in angiogenesis, and extracellular matrix turnover. Of these, Cathepsin S, CXCL10, FasL, ferritin, macrophage migration inhibitory factor (MIF), and resistin were also significantly elevated within LN kidneys. Conclusion Targeted urinary proteomics have uncovered multiple novel biomarkers for LN. Further validation in prospective cohorts and mechanistic studies are warranted to establish their clinical utility.

Urinary Cellular Profile as a Biomarker for Lupus Nephritis.

A search for the ideal biomarker for lupus nephritis (LN) is still underway, one that can be used for early detection and correlate with the class and activity of LN. Urine is normally devoid of leukocytes; however, it has been observed that macrophages and T lymphocytes are routinely present in the urine of LN patients and those with other proliferative renal diseases. This provides the idea for their potential use as biomarkers for proliferative LN. Here, we measured the urinary CD4+, CD8+ T lymphocytes, and CD14+ monocytes in patients with systemic lupus erythematosus (SLE) as potential biomarkers for LN. A longitudinal case-control study included 30 SLE patients with LN, 30 SLE patients without past or current LN, and 20 healthy subjects as a control group. The flow cytometric analysis was done using BD FACS Calibur multiparameter flow cytometer equipped with BD CellQuest Pro software for data analysis. CD14+ cells were the most abundant cells in the urine of LN patients. The mean numbers of urinary CD8+, CD4+, and CD14+ cells/mL were significantly higher in patients with LN than in those without. The cell counts correlated significantly with proteinuria. Urinary CD14+ cells seem to occur in much higher counts in class IV than class III LN. Urinary CD8+, CD4+, and CD14+ cells are highly sensitive and specific markers for detecting proliferative LN. A low CD4:CD8 ratio provides a further clue. Urinary CD14 cell counts may be a potential biomarker to differentiate between the different classes of proliferative LN.

Complements as a Predictive Biomarker of Lupus Nephritis in Female Patients with Systemic Lupus Erythematosus

Background: Lupus nephritis (LN) has been demonstrated in about 40–50 percent of all systemic lupus erythematosus (SLE) patients. Patients having renal flares are at risk from suffering serious kidney damage, and usually have a poor prognosis. Unfortunately, renal flare pathogenesis in LN patients remains unclear, and no known predictions of an impending renal flare exist. Aim: The present study aims to measure circulating levels of anti-C1q antibodies, C3, C4, TNF-α and soluble TNF-α receptor, serum creatinine and blood urea nitrogen (BUN) as biomarkers for active LN. Materials and methods: The study included 180 SLE female patients meeting the revised classification requirements of the modified American College of Rheumatology (ACR); 90 female patients with active proliferative LN (biopsy-proven) and other 90 patients with inactive LN. Patients were receiving mycophenolate mofetil; and the study was conducted between 2018 and 2019. Results: We found that low levels of complement C3 and C4 in combination with high levels of BUN, creatinine, anti-C1q antibodies and positive anti-dsDNA antibodies were more likely to be associated with lupus nephritis development in SLE patients. Also, high levels of TNF-α and its soluble receptor can be used as an indication of active disease activity and flare development. Conclusion: Monitoring of Anti-C1q antibodies, C3, C4, serum creatinine, and BUN levels in SLE patients can improve LN prognosis. TNF-α can also be used as an indicator for active LN and concomitant flare. This early diagnosis combined with prompt care would help decrease morbidity and mortality in LN patients.

Clinical and histological significance of urinary CD11c+ macrophages in lupus nephritis

BackgroundInfiltration of immune cells into the kidney is one of the key features of lupus nephritis (LN). The presence of immune cells in the urine may be used as a non-invasive biomarker of LN. Here, we aimed to analyze the clinicopathologic significance of urinary CD11c+ macrophages in patients with LN.MethodsThe numbers and proportions of CD11c+ macrophages in the urine samples of patients with LN at the time of kidney biopsy were examined using flow cytometry. We also examined the association between the levels of urinary CD11c+ macrophages and the clinical and pathologic features of patients with LN.ResultsCompared with patients without LN or those with non-proliferative LN, patients with proliferative LN had significantly higher numbers and proportions of urinary CD11c+ macrophages, which were strongly correlated with the serum anti-dsDNA antibody titer. The numbers and proportions of urinary CD11c+ macrophages were significantly associated with the values of chronicity indices such as tubular atrophy and interstitial fibrosis. No significant relationships were found between the levels of urinary CD11c+ macrophages and the activity scores, degree of proteinuria, or lupus disease activity. Urinary CD11c+ macrophages were more abundant in patients who did not achieve renal response to induction treatment with immunosuppressants than in those who achieved complete or partial response. The receiver operating characteristic (ROC) curve analysis showed that the number of urinary CD11c+ macrophages was the most powerful predictor of renal response at 6 months (ROC-AUC = 1.00, p = 0.0004).ConclusionThe urinary levels of CD11c+ macrophages were closely associated with the chronic pathologic changes of LN and renal response and may thus be used as a novel biomarker in LN.

Long Non-Coding RNAs as New Biomarkers in Lupus Nephritis: A Connection Between Present and Future.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). LN often leads to kidney failure, affecting the quality of a patient's life. There are several classical biomarkers that assist nephrologists’ daily practice. For more than 50 years, anti-double stranded DNA antibodies and complement components C3 and C4 have been used for LN disease activity evaluation. The major obstacle in the usage of conventional biomarkers is that none of them have both high specificity and high sensitivity. Moreover, an invasive kidney biopsy is still the gold standard for renal involvement detection in SLE patients. Therefore, new non-invasive biomarkers are needed for the early and accurate establishment of LN. Among the promising candidates are long non-coding RNAs (lncRNAs). Their dysregulation appears to have predictive and diagnostic potential. Furthermore, these biomarkers like other conventional biomarkers give insight into the pathogenesis of LN. This review aims to summarize the available information on lncRNAs in SLE patients and to present their future opportunities to add to the conventional biomarkers in the diagnosis and monitoring of LN.

Urine and serum S100A8/A9 and S100A12 associate with active lupus nephritis and may predict response to rituximab treatment

BackgroundApproximately 30% of patients with the systemic autoimmune/inflammatory disorder systemic lupus erythematosus (SLE) develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably...