Urinary cytokines and mRNA expression as biomarkers of disease activity in lupus nephritis (original) (raw)
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Arthritis research & therapy, 2015
Urinary T cells represent a reliable noninvasive biomarker for proliferative Lupus nephritis (LN). Little is known about the presence of T cell subsets, B cells and macrophages in the urine although they may further improve the validity of urinary cellular biomarkers for LN. We analyzed contemporaneous blood and urine samples of patients with active LN (n = 19), other Systemic Lupus Erythematosus (SLE) patients (n = 79) and urine samples of patients with diabetic nephropathy (DN; n = 14) and anti-neutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV; n = 11) by flow cytometry. Numbers of urinary T cells, B cells and macrophages correlated with disease activity and were significantly higher in the active LN group. Urinary T cells showed excellent distinction of patients with active LN, CD8+ T cells (AUC of ROC = 1.000) and CD4+ T cells (AUC = 0.9969) alike. CD19+ B cells (AUC = 0.7823) and CD14+ macrophages (AUC = 0.9066), as well as the clinical standard proteinuria (A...
Urinary CD4 + , CD8 + , CXCR3 + T cells and IL10 cells in lupus nephritis patients
Among the most promising novel biomarkers are molecules involved in the recruitment of cells into the kidney and molecules reflecting renal inflammation (cytokines). Prominent examples are urinary CXCL motif and IL10. The aim of the present work is to measure urinary CD4+, CD8+, chemokine receptor (CXCR3+) and interleukine 10 (IL10) in Lupus nephritis patients by flow cytometry in urine sample from 50 patients with LN and 22 healthy controls and correlate these urinary biomarkers with histological class, activity index and chronicity index. The results showed significant increase in CD4+, CD4+/CD8+, CXCR3+ and IL10 in urine of LN but significant decrease in CD8+. CXCR3+ is negatively correlated with activity index and chronicity index.
Background:- Although renal biopsy is the most accurate method for assessing renal inflammation in patients with lupus nephritis (LN), the technique is invasive and cannot be performed frequently. There is a critical need to identify biomarkers for systemic lupus erythematosus (SLE) which has a high prevalence of renal failure. Objective:- Our objective was to evaluate the level of urinary CD4 T-cells as a biomarker of active LN and indicator of treatment response in patients with SLE compared with normal control and its correlation with disease activity. Subjects and methods:- 64 patients with SLE and 20 age & sex matched control group were included. Patients were classified into two groups A & B. Group A with LN and moderate to severe SLE disease activity, Group B without LN and mild to inactive SLE. Levels of urinary CD4 T-cell were quanti?ed using ?ow cytometry in both patients\' groups and controls at baseline and repeated for patients\' groups only after 6 months. Results:- We found that CD4 T-cell level in Group (A) was significantly higher at baseline than in Group (B). There was significant decrease in the CD4 T-cell number in group A, when repeated after 6 months. Number of CD4 T- cells was correlated significantly with the disease activity both at baseline and after 6 months. In healthy controls, the urine was almost devoid of CD4T-cells. Conclusion:- Urinary CD4 T-cells is a good non-invasive marker for detecting active LN in SLE patients and also is a good monitor for treatment efficacy.
Bulletin of Egyptian Society for Physiological Sciences
Background: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by complex clinical manifestations and chronic inflammatory processes with failure of immunoregulatory mechanisms. Kidney is one of the most commonly affected organs. Considering the morbidity associated with SLE and particularly with lupus nephritis (LN), it is important to identify novel biomarkers of disease activity which could aid in the detection and assessment of flares and degree of activity. At present, activity of SLE is assessed based on clinical symptoms and biochemical parameters such as autoantibody (e.g antinuclear antibody (ANA)) and serum complement. However, these biomarkers are not specific for evaluating renal activity. Renal biopsy is the gold standard for assessment of kidney damage and disease activity, but its usage is restricted as it is an invasive procedure. Aim of the work: In the present study, plasma level of advanced oxidation protein products (AOPPs) and peripheral blood mononuclear cells nuclear factor-κB (PBMCs NF-κB) level as well as serum levels of fetuin-A, 25-hydroxyvitamin D (25OHD), calcium (Ca), inorganic phosphate were studied as novel biomarkers of LN activity and progression. Methods: The study included 30 SLE female patients, 15 without nephritis (group II) and 15 with nephritis (group III), in addition to 15 agematched healthy controls (group I). Overnight fasting blood was collected from all subjects for measurement of plasma AOPPs level, PBMCs NF-κB level and serum fetuin-A level, 25OHD level, Ca and inorganic phosphate levels as well as calculation of calcification risk index (CRI). Results: Plasma AOPPs, PBMCs NF-κB, serum inorganic phosphate levels and CRI were significantly higher in SLE patients (group II) than age-matched healthy controls (group I) (p<0.05) with the highest level in patients with LN (group III) meanwhile, serum fetuin-A and 25OHD levels were significantly lower in SLE patients than age-matched healthy controls (p<0.05) with the lowest level in LN patient group. In addition plasma AOPPs, PBMCs NF-κB levels and CRI showed significantly positive correlation meanwhile, fetuin-A and 25OHD levels showed significantly negative correlation with serum creatinine, 24 hours urinary albumin, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), ANA, anti double stranded DNA (Anti-dsDNA) antibodies levels and SLE disease activity index (SLEDAI). Conclusions: In SLE patients, high PBMCs NF-κB and plasma AOPPs levels as well as CRI while low levels of fetuin-A and 25OHD were related to disease activity and progression.
American Journal of Nephrology, 2021
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 utili...
Nephrology Dialysis Transplantation, 2006
Background. Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis. Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response. Results. Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-b), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-g) after immunosuppressive treatment, although the change of IFN-g was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-g (r ¼ 0.43, P ¼ 0.009), T-bet (r ¼ 0.40, P ¼ 0.016), TGF-b (r ¼ 0.51, P ¼ 0.002) and MCP-1 (r ¼ 0.38, P ¼ 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-g (r ¼ 0.45, P ¼ 0.009), T-bet (r ¼ 0.37, P ¼ 0.034), IL-10 (r ¼ 0.59, P<0.001), TGF-b (r ¼ 0.44, P ¼ 0.010) and MCP-1 (r ¼ 0.49, P ¼ 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period. Conclusions. The mRNA expression of T-bet, IL-10, TGF-b, MCP-1, and probably IFN-g in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity.
Role of Urinary Biomarkers for Diagnosis of Lupus Nephritis
Journal of Clinical & Experimental Pathology, 2018
Systemic lupus erythematosus (SLE) patients are having significant morbidity and mortality due to lupus nephritis (LN). To early management of lupus nephritis, these biomarkers have advantageous on the prognosis of LN. Kidney biopsy can be associated with significant morbidity, not possible carry out serially. Furthermore; renal biopsy may have sampling error because of extent number of glomeruli obtained for LN activity and chronicity. For diagnosis and observe of LN, there is always a need to find a non-invasive, easily available, and precise marker that can be followed continuously. The urinary biomarkers may be of such category. Routine clinical variable such as creatinine clearance, proteinuria, urine sediments, antids DNA, and complement levels are not sufficient for diagnosis of progressive disease activity in the LN and early regression of nephritis. Therefore, innovative biomarkers are compulsory to increase the diagnostic precision and sensitivity of lupus kidney disease, prognostic thesaurus, observing of treatment response, and identification of early kidney flares. In the index paper we reviewed recently discovered urinary biomarker in comparison to serum biomarker and kidney biopsy in LN.
A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies
Kidney International, 2012
The initial treatment of lupus nephritis is usually based on a renal biopsy. Subsequent disease flares, however, are often treated without the benefit of kidney pathology because repeat biopsies are infrequent. A noninvasive, real-time method to assess renal pathology would be useful to adjust treatment and improve outcome. To develop such a method we collected urine samples at or close to the time of 64 biopsies from 61 patients with lupus nephritis to identify potential biomarkers of tubulointerstitial inflammation and correlated these to biopsy parameters scored by a renal pathologist using a semiquantitative scale. Linear discriminant analysis was used to weight variables and derive composite biomarkers that identified the level of tubulointerstitial inflammation based on urine concentrations of monocyte chemotactic protein-1, hepcidin (a marker of active lupus), and liver fatty acid-binding protein. The discriminant function that described the most accurate composite biomarkers included urine monocyte chemotactic protein-1 and serum creatinine as the independent variables. This composite had sensitivity, specificity, positive predictive value, and negative predictive value of 100, 81, 67, and 100%, respectively. Only 14% of the biopsies were misclassified. Thus, specific renal pathologic lesions can be modeled by composite biomarkers to noninvasively follow and adjust the treatment of lupus nephritis reflecting renal injury.
Lupus, 2018
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. Aim To evaluate the plasma levels of a panel of cytokines and chemokines using multiplex xMAP technology in a cohort of Colombian patients with active and inactive systemic lupus erythematosus, and to evaluate their potential as biomarkers of renal involvement. Results Plasma from 40 systemic lupus erythematosus non-nephritis patients and 80 lupus nephritis patients with different levels of renal involvement were analyzed fo...