scholarly journals Immunoglobulin Binding Protein 1 as a Potential Urine Biomarker in Patients with Lupus Nephritis

2019 ◽  
Vol 20 (10) ◽  
pp. 2606 ◽  
Author(s):  
Eun-Ju Lee ◽  
Oh Chan Kwon ◽  
Byeongzu Ghang ◽  
Doo-Ho Lim ◽  
Do Hoon Kim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Human Peripheral Blood ◽  
Binding Protein ◽  
Clinical Activity ◽  
Immunoglobulin Binding Protein ◽  
Urine Biomarker ◽  
Immunoglobulin Binding

We evaluated the role of immunoglobulin binding protein 1 (IGBP1), a phosphoprotein associated with the B cell receptor (BCR) complex, as a urine biomarker in lupus nephritis (LN). The IGBP1 concentrations in plasma and urine of patients with LN, systemic lupus erythematosus (SLE) without nephritis and healthy controls were estimated by ELISA. IGBP1 expression in the kidneys of LN patients and transplantation donors was detected by immunohistochemistry. Microarray-based global gene expression profile of HK-2 cells with IGBP1 knock-down and fluorescence-activated cell sorting (FACS) for intracellular IGBP1 expression in human peripheral blood mononuclear cells (PBMCs) was performed. Urine IGBP1 levels were elevated significantly in LN patients, and it correlated with the clinical activity indices (complement 3 (C3) level, anti-dsDNA antibodies titer, SLE Disease Activity Index-2000 (SLEDAI-2K) and histological activity index. IGBP1 expression was increased in LN patients as compared to the donors and was detected mainly in the tubules by histopathology. In microarray analysis, several genes related to SLE pathogenesis (PPME1, ROCK2, VTCN1, IL-17R, NEU1, HLA-DM, and PTX3) responded to siRNA-mediated IGBP1 silencing. In FACS, IGBP1 was expressed mainly in the CD14+ cells. The overall expression of IGBP1 in PBMCs was higher in LN patients as compared with that in SLE patients without nephritis. Conclusively, urinary IGBP1 may be a novel biomarker reflecting the clinical and histological activities in LN.

scholarly journals Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus

2014 ◽  
Vol 142 (7-8) ◽  
pp. 431-436 ◽  
Author(s):  
Valentina Zivkovic ◽  
Aleksandra Stankovic ◽  
Tatjana Cvetkovic ◽  
Branka Mitic ◽  
Svetislav Kostic ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Activity ◽  
Systemic Lupus ◽  
Active Lupus Nephritis ◽  
Sensitivity Specificity

Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3?9.7 years on the average, with SLE of average duration 10.37?7.99 years, hospitalized at the Institute ?Niska Banja? during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p<0.01). SLE patients with SLEDAI ?11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p<0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79?83.46 U/ml vs. 57.81?63.15 U/ml; p<0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r=0.443; p<0.001), and anti-C1q antibodies (r=0.382; p<0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r=0.445; p<0.001). Conclusion. Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.

scholarly journals Insulin-Like Growth Factor Binding Protein-2 in Systemic Lupus Erythematosus Patients as a Marker of Lupus Nephritis Disease

2021 ◽  
pp. 1-13
Author(s):  
Zeinab N. ELRefeai ELgody ◽  
Ghadah Mahmoud Alghzaly ◽  
Mohammed Attia Saad Attia ◽  
Mohammed Mohammed Albedawey
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Growth Factor ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Systemic Lupus ◽  
Factor Binding ◽  
Significant Difference

Background: One of the members of Insulin-like Growth Factor Binding Protein family is IGFBP-2 that binds to the Insulin-like Growth Factor (IGF) receptors to regulate IGF biological activities. In nephrotic syndrome IGFBP-2 has also been reported to be increased in children and IGFBP-2 considers as predictor for longitudinal deterioration of kidney function in Type 2 Diabetes. The aim of the work was to assess insulin like growth factor binding protein-2 as a marker for activity of lupus nephritis. Methods: A cross-sectional study was carried out on 80 subjects and was divided on: Group1: 60 patients with Systemic lupus erythematosus which were subdivided into: (a) 40 Systemic lupus patients with nephritis. (b) 20 Systemic lupus patients without nephritis. Group 2: 20 healthy persons as control (Healthy controls). Results: there were statistically significant difference in ILGRFBPs2 P1, P2 while P3 was insignificant, Regarding the Systemic Lupus Erythematosus Disease Activity Index (SLEDI) score, there was significant difference between group IA and IB while statistically significant positive correlation between ILGFBPs2 and renal SLEDI score. Regarding ILGFBPs2, Anti-ds DNA Ab titer, renal biopsy classes and activity index, there was a statistically significant positive correlation. Regarding chronicity index and renal SLEDI score, there was insignificant correlation. Conclusion: Serum IGFBP‐2 is a promising biomarker for lupus nephritis, reflecting disease activity and chronicity changes in renal pathology.

Plasma immunoglobulin binding protein 1 as a predictor of development of lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 547-553
Author(s):  
Oh Chan Kwon ◽  
Eun-Ju Lee ◽  
Ji Seon Oh ◽  
Seokchan Hong ◽  
Chang-Keun Lee ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lupus Nephritis ◽  
Future Development ◽  
Predictive Value ◽  
Cox Regression ◽  
Binding Protein ◽  
Cox Regression Analysis ◽  
Dsdna Antibody ◽  
Immunoglobulin Binding Protein ◽  
Immunoglobulin Binding

Objective Urine levels of immunoglobulin binding protein 1 (IGBP1) are increased in patients with lupus nephritis (LN) compared with systemic lupus erythematosus (SLE) patients without nephritis. However, the clinical significance of IGBP1 level in plasma is unclear. We aimed to evaluate whether the plasma level of IGBP1 can predict future development of LN in SLE patients without nephritis. Methods Forty-three SLE patients without nephritis were followed for 5 years. Plasma IGBP1 levels were measured using ELISA, and clinical and laboratory data were obtained at study entry. Development of LN was confirmed by renal biopsy. Cox regression analysis was performed to identify factors associated with development of LN, and receiver operating characteristic curve analysis was used to determine the predictive value of each factor. Results Of the total 43 patients, eight (18.6%) developed LN during the follow-up period. Compared with patients who did not develop LN, those who developed LN had higher levels of plasma IGBP1 (6.3 ng/ml (range 4.3–9.6 ng/mL) vs. 13.3 ng/ml (range 7.2–31.3 ng/ml); p =  0.023). In the Cox regression analysis, higher CRP (hazard ratio (HR) = 1.325, 95% confidence interval (CI) 1.073–1.637, p =  0.009), anti-dsDNA antibody (Ab; HR = 1.066, 95% CI 1.012–1.124, p =  0.017) and plasma IGBP1 (HR = 1.091, 95% CI 1.034–1.152, p =  0.002) were associated with future development of LN. Among these factors, anti-dsDNA Ab (area under the curve (AUC)=0.893) had the highest predictive value followed by plasma IGBP1 (AUC = 0.761) and CRP (AUC = 0.634). A combination of anti-dsDNA Ab and plasma IGBP1 as a composite predictor was highly specific (97%) for predicting the development of LN. Conclusions Plasma IGBP1 can be used complementarily with anti-dsDNA Ab for detecting SLE patients at a higher risk of developing LN.

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

scholarly journals Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2516-2525 ◽  
Author(s):  
K Meszaros ◽  
S Aberle ◽  
R Dedrick ◽  
R Machovich ◽  
A Horwitz ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Binding Protein ◽  
Mononuclear Phagocytes ◽  
Factor Vii ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Fragment

Abstract Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (&gt; or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

scholarly journals Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients

2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Left Kidney ◽  
Renal Pathology ◽  
Class Iii ◽  
Stage Renal Disease ◽  
End Stage ◽  
Active Inflammation ◽  
Histological Results

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

Corrigendum to “Protection of mice against H. somni septicemia by vaccination with recombinant immunoglobulin binding protein subunits” [Vaccine 26 (2008) 4506–4512]

Vaccine ◽  
2012 ◽  
Vol 30 (30) ◽  
pp. 4578
Author(s):  
Roger S. Geertsema ◽  
Carolyn Worby ◽  
Robert P. Kruger ◽  
Yuichi Tagawa ◽  
Riccardo Russo ◽  
...  
Keyword(s):  
Binding Protein ◽  
Protein Subunits ◽  
Immunoglobulin Binding Protein ◽  
Immunoglobulin Binding

Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2161-2165 ◽  
Author(s):  
J Barbado ◽  
S Tabera ◽  
A Sánchez ◽  
J García-Sancho
Keyword(s):  
Lupus Nephritis ◽  
Mesenchymal Stromal Cells ◽  
Lupus Erythematosus ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Disease Activity Index ◽  
Controlled Clinical Trial ◽  
Allogeneic Mscs

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50–90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

Sign in / Sign up

Export Citation Format

Share Document