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Lupus nephritis biomarkers

Najla Aljaberi, Michael Bennett, Hermine I Brunner, Prasad Devarajan
Lupus nephritis (LN) is a common and significant manifestation, affecting 60% of adults and 80% of children with systemic lupus erythematosus, with up to 30% of patients progressing to end stage renal disease. There remains an unmet need for non-invasive markers of disease activity, damage, and response to therapy. In addition, non-invasive biomarkers that predict therapeutic efficacy are needed to enable cost-effective clinical trials of novel agents. Areas covered: This review examines the methodological aspects of urinary proteomics, the role of proteome profiling in identifying promising urinary biomarkers in LN, and the translation of research findings into clinically useful tools in the management of LN...
March 11, 2019: Expert Review of Proteomics
M Marín-Rosales, A Cruz, D C Salazar-Camarena, E Santillán-López, N Espinoza-García, J F Muñoz-Valle, M G Ramírez-Dueñas, E Oregón-Romero, G Orozco-Barocio, C A Palafox-Sánchez
B cell-activating factor (BAFF) promotes the survival, proliferation and maturation of B lymphocytes, which are key elements in the pathogenesis of systemic lupus erythematosus (SLE). This cytokine is encoded on TNFSF13B gene, and diverse single-nucleotide polymorphisms have been associated with susceptibility in different autoimmune disorders. In this study, the relationship of TNFSF13B gene rs9514827T>C, rs1041567T>A and rs9514828C>T polymorphisms, mRNA expression and soluble BAFF levels was investigated in 175 SLE patients and 208 healthy controls (HC)...
February 11, 2019: Clinical and Experimental Medicine
Kerstin Sandholm, Barbro Persson, Lillemor Skattum, Gösta Eggertsen, Dag Nyman, Iva Gunnarsson, Elisabet Svenungson, Bo Nilsson, Kristina N Ekdahl
Objectives: C1q is a valuable biomarker of disease activity in systemic lupus erythematosus (SLE). The "gold standard" assay, rocket immunoelectrophoresis (RIE), is time-consuming, and thus a shift to soluble immune precipitation techniques such as nephelometry has occurred. However, quantification of C1q with these techniques has been questioned as a result of the antibody binding properties of C1q. In the present work, we have compared results using various techniques (RIE, nephelometry, and ELISA) and have developed and validated a new magnetic bead-based sandwich immunoassay (MBSI)...
2019: Frontiers in Immunology
Akimitsu Kitagawa, Naotake Tsuboi, Yuki Yokoe, Takayuki Katsuno, Hidekazu Ikeuchi, Hiroshi Kajiyama, Nobuhide Endo, Yuriko Sawa, Junya Suwa, Yutaka Sugiyama, Asaka Hachiya, Toshihide Mimura, Keiju Hiromura, Shoichi Maruyama
Noninvasive biomarkers of disease activity are needed to monitor response to therapy and predict disease recurrence in patients with glomerulonephritis. The leukocyte surface markers integrin Mac-1 and CD16b have been implicated in the pathogenesis of lupus nephritis (LN). Mac-1 comprises a unique α subunit (CD11b) complexed with a common β2 subunit, which are released along with CD16b from specific leukocyte subsets under inflammatory conditions including glomerulonephritis. We investigated the association of urinary CD11b and CD16b with histopathological activity in 272 patients with biopsy-proven glomerular diseases, including 118 with LN...
January 26, 2019: Kidney International
A A Gasparin, N Pamplona Bueno de Andrade, V Hax, G Leví Tres, F J Veríssimo Veronese, O A Monticielo
Renal involvement is one of the main complications of systemic lupus erythematosus, causing a significant impact on patients' morbidity and mortality. Renal biopsy is still the gold standard of diagnosis, but it has many limitations. In this sense, several recent studies aim to identify biomarkers that not only predict disease activity and renal histology, but also lead to earlier treatment. In previous studies, the soluble vascular cell adhesion molecule-1 measured in urine showed a strong association with the presence of lupus nephritis, with clinical and histological activity indexes of the disease and with more severe renal lesions...
February 2, 2019: Lupus
Brad H Rovin, Dawn J Caster, Daniel C Cattran, Keisha L Gibson, Jonathan J Hogan, Marcus J Moeller, Dario Roccatello, Michael Cheung, David C Wheeler, Wolfgang C Winkelmayer, Jürgen Floege
In November 2017, the Kidney Disease: Improving Global Outcomes (KDIGO) initiative brought a diverse panel of experts in glomerular diseases together to discuss the 2012 KDIGO glomerulonephritis guideline in the context of new developments and insights that had occurred over the years since its publication. During this KDIGO Controversies Conference on Glomerular Diseases, the group examined data on disease pathogenesis, biomarkers, and treatments to identify areas of consensus and areas of controversy. This report summarizes the discussions on primary podocytopathies, lupus nephritis, anti-neutrophil cytoplasmic antibody-associated nephritis, complement-mediated kidney diseases, and monoclonal gammopathies of renal significance...
February 2019: Kidney International
M A El-Gamasy, W El-Naghy
One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls...
November 2018: Indian Journal of Nephrology
Yi-Jung Li, Hsin-Hsu Wu, Shou-Hsuan Liu, Kun-Hua Tu, Cheng-Chia Lee, Hsiang-Hao Hsu, Ming-Yang Chang, Kuang-Hui Yu, Wei Chen, Ya-Chung Tian
OBJECTIVE: Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE). METHODS: Ninety patients with SLE were divided into biopsy-proven LN (n = 54) and no kidney involvement (non-LN) (n = 36) groups and followed up for 54 months. RESULTS: Of 36 patients with LN, 3 (5.6%) had class II disease, 3 (5...
2019: PloS One
Hui Zhao, Shi-Xing Ma, You-Quan Shang, Huan-Qiao Zhang, Wei Su
Chronic kidney disease (CKD) results in high morbidity and mortality worldwide causing a huge socioeconomic burden. MicroRNA (miRNA) exert critical regulatory functions by targeting downstream genes and have been associated with many pathophysiologic processes including CKD. In fact, many studies have shown that the expression of various miRNAs was significantly changed in CKD. Current investigations have focused on revealing the relationship between miRNAs and CKD states including diabetic nephropathy, lupus nephritis, focal segmental glomerulosclerosis and IgA nephropathy...
January 10, 2019: Clinica Chimica Acta; International Journal of Clinical Chemistry
Samantha Stanley, Chi Chiu Mok, Kamala Vanarsa, Deena Habazi, Jennifer Li, Claudia Predoza, Ramesh Saxena, Chandra Mohan
OBJECTIVE: To identify low abundance urinary protein biomarkers in Lupus nephritis (LN), this study aims to investigate the utility of a more sensitive platform using electrochemiluminescence (ECL). METHODS: 48 human urine samples across 2 independent cohorts (each matched for age/gender/race and containing 8 active LN (rSLEDAI>0), 8 inactive lupus (rSLEDAI=0), and 8 healthy controls) were tested using a pre-existing 40-plex ECL panel. A custom 5-plex ECL panel was then developed for further validation studies and used to test 140 urine samples...
January 7, 2019: Arthritis & Rheumatology
Chenglong Fang, Tingting Luo, Ling Lin
Background: Systemic lupus erythematosus (SLE) patients have tendencies of accelerated atherosclerosis (AS) which can only partly be explained by traditional cardiovascular disease (CVD) risk factors. Imbalanced inflammation also plays a vital role. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new therapeutic target for AS for its dual mechanisms in lipids and inflammation. We aimed to assess serum PCSK9 concentrations in SLE patients and its possible role in atherogenesis of SLE...
December 2018: Annals of Translational Medicine
W A Wan Asyraf, M S Mohd Shahrir, W Asrul, A W Norasyikin, O Hanita, W Y Kong, M T Azmi
Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis...
December 20, 2018: Reumatismo
Catalina Burbano, Jóse A Gómez-Puerta, Carlos Muñoz-Vahos, Adriana Vanegas-García, Mauricio Rojas, Gloria Vásquez, Diana Castaño
Non-classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated...
February 2019: European Journal of Immunology
Veronica G Anania, Kebing Yu, Francesco Pingitore, Qingling Li, Christopher M Rose, Peter Liu, Wendy Sandoval, Ann E Herman, Jennie R Lill, W Rodney Mathews
Lupus nephritis (LN) is a severe clinical manifestation of systemic lupus erythematosus (SLE) associated with significant morbidity and mortality. Assessment of severity and activity of renal involvement in SLE requires a kidney biopsy, an invasive procedure with limited prognostic value. Non-invasive biomarkers are needed to inform treatment decisions and to monitor disease activity. Proteinuria is associated with disease progression in LN, however, the composition of the LN urinary proteome remains incompletely characterized...
December 10, 2018: Journal of Proteome Research
Qingyan Liu, Jiao Fan, Jing Bai, Liang Peng, Tao Zhang, Lei Deng, Gaokun Wang, Yu Zhao, Jingguo Nong, Minghua Zhang, Yu Wang
Atherosclerosis is characterized as a chronic inflammatory disease and macrophage-derived foam cells play a central role during the pathologic processes. A newly discovered cytokine interleukin-34 (IL-34) is closely associated with various inflammatory and autoimmune diseases. Expression of IL-34 in obesity, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), lupus nephritis and coronary artery diseases (CAD) are significantly elevated. However, the role of IL-34 in atherosclerosis remains unknown...
November 26, 2018: Scientific Reports
L Pacheco-Lugo, J Sáenz-García, E Navarro Quiroz, H González Torres, L Fang, Y Díaz-Olmos, G Garavito de Egea, E Egea Bermejo, G Aroca Martínez
BACKGROUND: Systemic lupus erythematosus is a heterogeneous chronic inflammatory autoimmune disorder characterized by an exacerbated expression of cytokines and chemokines in different tissues and organs. Renal involvement is a significant contributor to the morbidity and mortality of systemic lupus erythematosus, and its diagnosis is based on renal biopsy, an invasive procedure with a high risk of complications. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with systemic lupus erythematosus is a priority...
November 19, 2018: Lupus
Khedidja Bouachi, Anissa Moktefi, Shao-Yu Zhang, Julie Oniszczuk, Kelhia Sendeyo, Philippe Remy, Vincent Audard, Andre Pawlak, Mario Ollero, Djillali Sahali
Lupus glomerulopathies are classified into various histological patterns, which probably result from different pathophysiological origins. Podocyte injury can be demonstrated in lupus nephritis but its clinical relevance is far little appreciated and is often masked by proliferative lesions and inflammatory cell infiltrations. Two patterns of podocyte lesions may be considered, either occurring in the context of renal inflammation or reflecting podocyte dysfunction in non-proliferative and non-inflammatory glomerulopathies...
2018: PloS One
Majid Khoshmirsafa, Nahid Kianmehr, Reza Falak, Seyed Javad Mowla, Farhad Seif, Behnaz Mirzaei, Mohadeseh Valizadeh, Mehdi Shekarabi
AIM: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). There is a great interest in using microRNAs (miRNAs) as diagnostic and prognostic biomarkers in autoimmune diseases. MATERIALS AND METHODS: This study evaluated miR-16, miR-21, miR-141, miR-146a, and miR-155 expression levels in peripheral blood mononuclear cells (PBMCs) of 55 female SLE patients with absent, inactive, or active nephritis, and 30 healthy controls (HCs) using quantitative polymerase chain reaction...
November 5, 2018: International Journal of Rheumatic Diseases
Fabien B Vincent, Laura Slavin, Alberta Y Hoi, Arthur Richard Kitching, Fabienne Mackay, James Harris, Rangi Kandane-Rathnayake, Eric F Morand
Objective: To characterise the clinical relevance of urinary macrophage migration inhibitory factor (uMIF) concentrations in patients with systemic lupus erythematosus (SLE). Methods: MIF, adjusted for urine creatinine, was quantified by ELISA in urine samples from 64 prospectively recruited patients with SLE. Serum MIF and urinary monocyte chemoattractant protein 1 (uMCP-1) were quantified by ELISA in a subset of patients (n = 39). Disease activity was assessed using the SLE Disease Activity Index-2000 (SLEDAI-2K) score...
2018: Lupus Science & Medicine
E M D Smith, A Eleuteri, B Goilav, L Lewandowski, A Phuti, T Rubinstein, D Wahezi, C A Jones, S D Marks, R Corkhill, C Pilkington, K Tullus, C Putterman, C Scott, A C Fisher, M W Beresford
BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort...
November 2, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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