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Lupus nephritis biomarkers

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 non-pregnant and 36 pregnant women with SLE (test groups) and 60 non-pregnant 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...
July 31, 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...
July 18, 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...
July 28, 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...
June 29, 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...
January 1, 2018: Lupus
Helena Idborg, Susanna Eketjäll, Susanne Pettersson, Johanna T Gustafsson, Agneta Zickert, Marika Kvarnström, Vilija Oke, Per-Johan Jakobsson, Iva Gunnarsson, Elisabet Svenungsson
Objectives: Composite criteria/indices are presently used to diagnose and monitor patients with systemic lupus erythematosus (SLE). Biomarkers for these purposes would be helpful in clinical practice. We therefore evaluated a large panel of cytokines and basic laboratory tests and investigated their performance as discriminators versus controls and as biomarkers of disease activity (DA). Methods: We examined 437 patients with SLE, fulfilling American College of Rheumatology-82 criteria, and 322 matched controls...
2018: Lupus Science & Medicine
Yanyun Wang, Ye Tao, Yi Liu, Yi Zhao, Chao Song, Bin Zhou, Tao Wang, Linbo Gao, Lin Zhang, Huaizhong Hu
The current methods of monitoring the activity of lupus nephritis (LN) may cause unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to find a urinary biomarker that could be developed as a home-based test for monitoring the activity of LN.Urine samples were collected immediately before a renal biopsy from patients of suspected active LN, and also from patients with inactive LN, systemic lupus erythematous without LN or healthy controls. Biomarker search was conducted on a cytokine antibody array and confirmation was done by quantitative evaluation with enzyme-linked immunosorbent assay...
June 2018: Medicine (Baltimore)
Anupam Guleria, Sanat Phatak, Durgesh Dubey, Sandeep Kumar, Abhishek Zanwar, Smriti Chaurasia, Umesh Kumar, Ranjan Gupta, Amita Aggarwal, Dinesh Kumar, Ramnath Misra
Lupus nephritis (LN) is a major cause of morbidity and mortality in lupus. Renal biopsy is the gold standard for classification of nephritis, but because of its impracticality, new approaches for improving patient prognostication and monitoring treatment efficacy are needed. We aimed to evaluate the potential of metabolic profiling in identifying biomarkers to distinguish disease and monitor treatment efficacy in patients with LN. Serum samples from patients with LN ( n = 18) were profiled on NMR-based metabolomics platforms at diagnosis and after 6 months of treatment...
July 6, 2018: Journal of Proteome Research
Y Zhang, Y Wang
OBJECTIVE: To investigate whether plasma microRNA-200 family expressions could serve as diagnostic biomarkers in patients with lupus nephritis (LN), and their association with disease severity. PATIENTS AND METHODS: 101 adult LN patients and 100 adult health volunteers were recruited in our study. A blood sample was obtained from all participants, and total RNA was extracted from plasma. Real-time PCR was performed to evaluate the relative expression of microRNA (miRNA)...
May 2018: European Review for Medical and Pharmacological Sciences
Christian Goess, Christopher M Harris, Sara Murdock, Richard W McCarthy, Erik Sampson, Rachel Twomey, Suzanne Mathieu, Regina Mario, Matthew Perham, Eric R Goedken, Andrew J Long
OBJECTIVES: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease. METHODS: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays. The impact of ABBV-105 on B cell function in vivo was assessed using mechanistic models of antibody production...
July 23, 2018: Modern Rheumatology
Yingpeng Ren, Jing Xie, Feng Lin, Wanwan Luo, Zhencheng Zhang, Panying Mao, Renqian Zhong, Yan Liang, Zaixing Yang
BACKGROUND: It has been demonstrated that serum human epididymis protein 4 (HE4) is a useful biomarker for differentiating lupus nephritis (LN) from systemic lupus erythematosus (SLE). However, it remains unclear whether HE4 can be used to predict the development of LN. METHODS: A total of 74 SLE patients without LN were recruited between August 2008 and September 2013. Serum HE4 concentrations were measured by enzyme-linked immunosorbent assay. These patients were followed up from the date of SLE diagnosis to LN development or the end of the study...
July 2018: International Immunopharmacology
Joan E Wither, Stephenie D Prokopec, Babak Noamani, Nan-Hua Chang, Dennisse Bonilla, Zahi Touma, Carmen Avila-Casado, Heather N Reich, James Scholey, Paul R Fortin, Paul C Boutros, Carolina Landolt-Marticorena
Both a lack of biomarkers and relatively ineffective treatments constitute impediments to management of lupus nephritis (LN). Here we used gene expression microarrays to contrast the transcriptomic profiles of active SLE patients with and without LN to identify potential biomarkers for this condition. RNA isolated from whole peripheral blood of active SLE patients was used for transcriptomic profiling and the data analyzed by linear modeling, with corrections for multiple testing. Results were validated in a second cohort of SLE patients, using NanoString technology...
2018: PloS One
S Qi, Q Chen, D Xu, N Xie, Y Dai
Systemic lupus erythematosus (SLE) is a type of autoimmune disease that damages multiple organs, including the heart, joints, liver and kidneys. The main characteristics of SLE are the deposition of circulating autoantibodies; autoantigen complexes in the renal system; and abnormal expression of complements, cytokines and chemokines. Lupus nephritis (LN) is the most serious manifestation of SLE and is characterized by inflammation of the kidney. This review summarizes recent clinical applications of protein biomarkers including autoantibodies, complements, cytokines and chemokines and some new protein biomarkers in SLE and LN...
January 1, 2018: Lupus
Xiwen Dong, Zhaohui Zheng, Xing Luo, Jin Ding, Ying Li, Zhiqin Li, Sijia Li, Mengyao Rong, Yalu Fu, Zhenbiao Wu, Ping Zhu
The aim of this study was to determine whether combined utilization of untimed single urine monocyte chemoattractant protein 1 (uMCP-1) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (uTWEAK) could serve as a screening test for proteinuria in patients with lupus nephritis (LN).A case-control study that contained 39 biopsy-proven LN patients, 20 non-LN systemic lupus erythematosus (SLE) patients, and 10 healthy controls (HCs) were carried out. Correlations between uMCP-1, uTWEAK, and traditional clinical markers were analyzed by Spearman correlation test...
April 2018: Medicine (Baltimore)
Nima Tanha, Renata Baronaite Hansen, Christoffer Tandrup Nielsen, Mikkel Faurschou, Søren Jacobsen
OBJECTIVE: In a longitudinal cohort study, we investigated whether clinical and serological manifestations at the time of classification of systemic lupus erythematosus (SLE) were predictive of subsequent development of incident proteinuria as a biomarker of incident lupus nephritis. METHODS: Patients fulfilling SLE classification criteria but having no proteinuria prior to or at the time of classification were included. Data on SLE manifestations, vital status, criteria-related autoantibodies, and SLE-associated medications were collected during clinical visits and supplemented by chart review...
July 2018: Journal of Rheumatology
Hege L Pedersen, Kjersti D Horvei, Dhivya Thiyagarajan, Gudrun E Norby, Natalya Seredkina, Gabriella Moroni, Gro Ø Eilertsen, Hallvard Holdaas, Erik H Strøm, Gunnstein Bakland, Pier-Luigi Meroni, Ole P Rekvig
Renal DNase I is lost in advanced stages of lupus nephritis. Here, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression. Mouse and human DNase I protein and DNase I endonuclease activity levels were determined by western blot, gel, and radial activity assays at different stages of the murine and human forms of the disease. Cellular localization of DNase I was analyzed by immunohistochemistry, immunofluorescence, confocal microscopy, and immunoelectron microscopy...
February 21, 2018: Journal of Pathology. Clinical Research
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