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Lupus nephritis biomarkers

Yi Li, Xiaosong Xu, Xiaopeng Tang, Xiuwu Bian, Bingbing Shen, Hongwen Zhao, Shiyuan Luo, Zhiwen Chen, Keqin Zhang
Background: Type IV lupus nephritis (LNIV) is a severe disease characterized by diffuse proliferative lesions, and its prognosis is worse with cellular crescent (LNIV-CC) involvement. Urinary exosomes have been shown to reflect the degree of kidney injury. This study was aimed to identify non-invasive diagnostic markers for LNIV-CC. We analysed the expression profile of microRNAs (miRNAs) isolated from urinary exosomes in patients with LNIV-CC and LNIV, and healthy individuals using high-throughput sequencing...
December 2018: Journal of Biological Research
Jessica L Turnier, Hermine I Brunner, Michael Bennett, Ashwaq Aleed, Gaurav Gulati, Wendy D Haffey, Sherry Thornton, Michael Wagner, Prasad Devarajan, David Witte, Kenneth D Greis, Bruce Aronow
Objectives: We used an unbiased proteomics approach to identify candidate urine biomarkers (CUBMs) predictive of LN chronicity and pursued their validation in a larger cohort. Methods: In this cross-sectional pilot study, we selected urine collected at kidney biopsy from 20 children with varying levels of LN damage (discovery cohort) and performed proteomic analysis using isobaric tags for relative and absolute quantification (iTRAQ). We identified differentially excreted proteins based on degree of LN chronicity and sought to distinguish markers exhibiting different relative expression patterns using hierarchically clustered log10-normalized relative abundance data with linked and distinct functions by biological network analyses...
October 4, 2018: Rheumatology
Fatma M Elsenosy, Sabila G Mousa, Nagwa A Mohamed, Rehab H Mohamed
Systemic Lupus Erythematosus (SLE) is a chronic and potentially fatal autoimmune disorder characterized by the production of auto-antibodies that cause widespread tissue damage. Validate Antichromatin antibodies as a biomarker of renal involvement in SLE and how their titers correlate with systemic lupus activity measure (SLAM) index among a sample of Egyptian systemic lupus patients. The study was conducted on 60 patients diagnosed according to ACR criteria for diagnoses of SLE (Group I) and 25 age matched healthy controls (Group II)...
January 2018: Egyptian Journal of Immunology
Yasser A Zaitoon, Abeer A Shehab, Nesrine A Mohamed, Caroline S Morad, Engy M Yassine
This study aimed to determine whether plasma soluble urokinase plasminogen activator receptor (suPAR) could serve as an activity biomarker in systemic lupus erythematosus (SLE) patients. suPAR levels were assessed in SLE patients, compared to healthy controls and correlated with disease activity. Sixty SLE patients were enrolled with assessment of disease activity using SLE Disease Activity Index (SLEDAI), C3, soluble urokinase plasminogen activator receptor level. Patients were divided according to disease activity into three groups: Patients in remission, mild to moderate activity, and high disease activity...
January 2018: Egyptian Journal of Immunology
Vinicius Domingues, Benjamin A Levinson, Nicole Bornkamp, Judith D Goldberg, Jill Buyon, H Michael Belmont
Objectives: The study aimed to determine if serum albumin at 12 months predicts long-term renal outcome at 48 months. Data from the NYU SAMPLE (Specimen and Matched Phenotype Linked Evaluation) Lupus Registry were used to compare the performance of albumin, anti-double-stranded DNA, C3/C4, proteinuria and haematuria. Methods: 82 patients with SLE with data at time of renal biopsy, at 12 months and at a second visit, and up to 48 months were included. The significance of each biomarker as a predictor of an adverse renal outcome (ARO), defined as doubling of serum creatinine, as creatinine >4 mg/dL if initial >2...
2018: Lupus Science & Medicine
W Cao, X Liu, X Xu, M Zeng, B Sun, X Yu, N Wang, H Mao, B Zhang, Y Yuan, C Xing
The Src homology and collagen A (ShcA) adaptor protein that binds to tyrosine kinase receptors. ShcA plays a role in insulin signaling, stress resistance and energy metabolism. The 66-kDa Src homology 2 domain-containing protein (p66shc) belongs to the ShcA family and has been associated with reactive oxygen species (ROS); increased ROS is involved in the pathology of lupus nephritis (LN). However, whether ShcA can act as a biomarker for oxidative injury in LN is unknown. This study is aimed to investigate the ShcA expression in kidney tissues from patients presenting with LN and the association between ShcA expression and clinical parameters...
September 6, 2018: Lupus
Dawn J Caster, Michael L Merchant, Jon B Klein, David W Powell
Patients with systemic lupus erythematosus frequently develop lupus nephritis (LN), a condition that can lead to end-stage kidney disease. Multiple serum and urine biomarkers for LN have been proposed in recent years, yet none have become incorporated into clinical use. The majority of studies have been single center with significant variability in cohorts, assays, and sample storage, leading to inconclusive results. It has become clear that no single biomarker is likely to be sufficient to diagnose LN, identify flares, and define the response to therapy and prognosis...
August 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Qingqing Ouyang, Qin Huang, Zhenlan Jiang, Jinjun Zhao, Guo-Ping Shi, Min Yang
This study aimed to determine the expression of circRNAs in plasma from lupus nephritis (LN) patients to identify novel biomarkers for LN screening. We initially performed microarray screening of circRNA changes in plasma from 5 L N patients, 5 systemic lupus erythematosus (SLE) patients without LN, and 5 healthy controls. We then confirmed the selected circRNA changes in plasma from 59 SLE patients (30 with LN and 29 without LN), 26 rheumatoid arthritis (RA) patients, and 27 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction...
September 2018: Molecular Immunology
Hermine I Brunner, Gaurav Gulati, Marisa S Klein-Gitelman, Kelly A Rouster-Stevens, Lori Tucker, Stacey P Ardoin, Karen B Onel, Rylie Mainville, Jessica Turnier, Pinar Ozge Avar Aydin, David Witte, Bin Huang, Michael R Bennett, Prasad Devarajan
OBJECTIVES: To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). METHODS: In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured...
August 29, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Ji-Yih Chen, Chin-Man Wang, Tai-Di Chen, Yeong-Jian Jan Wu, Jing-Chi Lin, Ling Ying Lu, Jianming Wu
BACKGROUND: Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. METHODS: TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan...
August 29, 2018: Arthritis Research & Therapy
Pattarin Tangtanatakul, Siriwan Klinchanhom, Pimpayao Sodsai, Thitima Sutichet, Chutipha Promjeen, Yingyos Avihingsanon, Nattiya Hirankarn
BACKGROUND: The contents of exosomes determine their biological functions and represent a new class of epigenetic modulation of renal cells considering as novel class of biomarker. OBJECTIVE: Our study aims to investigate the expression of microRNAs (miRNA), including miR-10a/b, let-7a, and miR-21, in urinary exosomes isolated from patients with active lupus nephritis (LN) compared to inactive LN. METHODS: The exosomes were obtained from long-term follow up LN patients during active and 4 months after treatment (n = 3)...
August 13, 2018: Asian Pacific Journal of Allergy and Immunology
Bogdan Jakiela, Joanna Kosałka, Hanna Plutecka, Stanisława Bazan-Socha, Marek Sanak, Jacek Musial
The objective of this study was to investigate the mechanisms of Th17 expansion in lupus nephritis (LN) patients, and determine whether it is associated with impaired function of regulatory T-cells (Treg). Major effector subsets of peripheral blood CD4+ T-cells were assessed by flow cytometry in 33 LN patients with different activity of the disease, and 19 healthy controls. Percentage of circulating Th17 cells was increased in LN (median 1.2% of CD4+ as compared to 0.6% in control group, P<0.01), while Treg cells remained unchanged (12...
August 7, 2018: Clinical and Experimental Immunology
Yalan Xu, Yijun Song, Jiazhen Chang, Xiya Zhou, Qingwei Qi, Xinping Tian, Mengtao Li, Xiaofeng Zeng, Mengnan Xu, Wenjuan Zhang, David S Cram, Juntao Liu
BACKGROUND: High levels of circulating cell-free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Comparative groups comprised 22 nonpregnant and 36 pregnant women with SLE (test groups) and 60 nonpregnant and 199 pregnant women with no history of SLE (control groups). The levels of cfDNA in plasma were quantitated by a fluorometric dsDNA assay...
August 5, 2018: European Journal of Clinical Investigation
Zdenka Hruskova, Vladimir Tesar
Treatment of systemic lupus erythematosus (SLE) represents a challenge due to variable disease manifestations, clinical course, and outcome. Long-term outcome in SLE remain unsatisfactory and a search for new therapeutic options is definitely warranted. Despite expectations, most clinical trials performed in SLE and lupus nephritis in the last decade did not reach primary outcome, and the only drug that has been licensed is belimumab. Areas covered: Results of negative trials testing monoclonal antibodies and other biologic agents in SLE are briefly summarized...
September 2018: Expert Opinion on Biological Therapy
Y Ding, L-M Nie, Y Pang, W-J Wu, Y Tan, F Yu, M-H Zhao
Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed...
October 2018: Lupus
Chantal Dumestre-Pérard, Giovanna Clavarino, Sophie Colliard, Jean-Yves Cesbron, Nicole M Thielens
Lupus nephritis (LN) is one of the most frequent and severe manifestations of systemic lupus erythematosus (SLE), considered as the major predictor of poor prognosis. An early diagnosis of LN is a real challenge in the management of SLE and has an important implication in guiding treatments. In clinical practice, conventional parameters still lack sensitivity and specificity for detecting ongoing disease activity in lupus kidneys and early relapse of nephritis. LN is characterized by glomerular kidney injury, essentially due to deposition of immune complexes involving autoantibodies against cellular components and circulating proteins...
September 2018: Autoimmunity Reviews
Huidi Zhang, Xixi Huang, Lulu Ye, Gangqiang Guo, Xiao Li, Chaosheng Chen, Li Sun, Baoqing Li, Nan Chen, Xiangyang Xue
Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls ( P  < 0...
2018: Frontiers in Immunology
Yu-Jih Su, I-Chun Lin, Lin Wang, Cheng-Hsien Lu, Yi-Ling Huang, Ho-Chang Kuo
The symptomatology of lupus nephritis (LN) consists of foamy urine and lower leg edema, as well as such systemic manifestations as oral ulcers, arthralgia/arthritis, and lymphadenopathy. However, these symptoms may appear mild and non-specific. If these symptoms are unrecognized, thus delaying treatment, approximately 10% of LN patients will develop permanent kidney damage and end-stage kidney disease. Therefore, the purpose of this study is to identify a surrogate biomarker for the early detection of LN. In this study, we first adopted next generation sequencing (NGS) in order to screen differential expression levels of microRNA between SLE patients with and without LN...
June 15, 2018: Oncotarget
Rubina Novelli, Ariela Benigni, Giuseppe Remuzzi
The damage and loss of podocytes is a primary hallmark of nephrotic syndrome. In the pursuit of targetable molecules that are involved in podocyte pathophysiology, some studies have identified B7-1 (also known as CD80) as a potential biomarker. Furthermore, B7-1 blockade has been proposed as a podocyte-specific treatment for patients with nephrotic syndrome who have limited therapeutic options, such as those with focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy and lupus nephritis...
September 2018: Nature Reviews. Nephrology
D J Go, J Y Lee, M J Kang, E Y Lee, E B Lee, E C Yi, Y W Song
Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure...
September 2018: Lupus
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