scholarly journals Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9854
Author(s):  
Ping Chen ◽  
Yan Chen ◽  
Maoqing Jiang ◽  
Yijun Mo ◽  
Huanhuan Ying ◽  
...  
Keyword(s):  
Minimal Change Disease ◽  
Minimal Change ◽  
Healthy Controls ◽  
Adult Onset ◽  
Gm Csf ◽  
Significant Difference ◽  
Cytokine Levels ◽  
Urine Concentrations ◽  
Age Range

Background Minimal change disease (MCD) is a common form of nephrotic syndrome in adults. However, the molecular mechanism underlying the pathogenesis of MCD remains incompletely understood. In this study, we aimed to investigate the role of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset MCD patients. Methods The lymphocyte subsets, 34 cytokine levels of Th1/Th2/Th17, serum and urine concentrations of CD80, and expression of CD80 in glomeruli were analyzed in 28 cases (15 males and 13 females; average age: 34.1 years, age range: 18–56 years), including 10 patients with MCD in relapse, nine patients with MCD in remission and nine healthy controls. Results There was no significant difference of CD3+CD4+ cells proportion among patients with MCD in relapse, MCD in remission and healthy controls (P = 0.802). The cytokine levels of GM-CSF and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) in patients with MCD in relapse increased 1.5 times higher than those in remission. An evident increase in the excretion of urinary CD80 was found in patients with relapsed MCD compared with those in remission (598.4 ± 115.8 vs 81.78 ± 7.04 ng/g creatinine, P < 0.001) and healthy controls (598.4 ± 115.8 vs 67.44 ±  8.94  ng/g creatinine, P < 0.001). CD80 expression was observed in podocyte of MCD patient in relapse by immunofluorescence technique. Conclusions The cytokines GM-CSF and TRANCE are increased and the urinary CD80 levels are elevated in adult-onset MCD patients in relapse, indicating a disorder of Th1/Th2/Th17 balance and that the elevated excretion of CD80 may underlie the pathogenesis and development of adult-onset MCD.

scholarly journals Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jiwon M. Lee ◽  
Jae Won Yang ◽  
Andreas Kronbichler ◽  
Michael Eisenhut ◽  
Gaeun Kim ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Minimal Change Disease ◽  
Meta Analysis ◽  
Minimal Change ◽  
Adult Patients ◽  
Healthy Controls ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Significant Difference ◽  
Plasminogen Activator Receptor

Introduction. The soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS. Methods. Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Results. A total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants=814; studies=9, I2=85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference. Conclusions. Our meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.

scholarly journals IgM Mesangial Deposition Predicts Relapses of Adult-Onset Minimal Change Disease

2020 ◽  
Author(s):  
Cheng-Wen Yang ◽  
Fan-Yu Chen ◽  
Fu-Pang Chang ◽  
Yang Ho ◽  
An-Hang Yang ◽  
...  
Keyword(s):  
Minimal Change Disease ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Treatment ◽  
Minimal Change ◽  
Immunoglobulin M ◽  
Response To Treatment ◽  
Adult Onset ◽  
Significant Difference ◽  
The Impact

Abstract Background: Immunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence regarding the impact of IgM mesangial deposition on the treatment responses or outcomes in adult-onset MCD is lacking.Methods: In this retrospective cohort study, 37 adult patients with MCD received kidney biopsy from January 2010 to May 2020. According to IgM mesangial deposition by immunofluorescence microscopy, the patients were divided into two groups (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for two years between the two groups.Results: Regarding the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission, there was no statistically significant difference between the two groups. Compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group within the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116-0.784, p = 0.010).Conclusions: Our findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, prolonged and combined immunosuppressive therapy with close follow-up may be considered in MCD adults with IgM mesangial deposition.

scholarly journals Clinical Characteristics and Outcomes of Adults with Nephrotic Syndrome Due to Minimal Change Disease

2021 ◽  
Vol 10 (16) ◽  
pp. 3632
Author(s):  
Sophia Lionaki ◽  
Evangelos Mantios ◽  
Ioanna Tsoumbou ◽  
Smaragdi Marinaki ◽  
George Makris ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Minimal Change Disease ◽  
Kidney Injury ◽  
Spontaneous Remission ◽  
Minimal Change ◽  
Adult Onset ◽  
Potential Risk Factors ◽  
The Mean ◽  
End Stage

Purpose: Minimal change disease (MCD) is considered a relatively benign glomerulopathy, as it rarely progresses to end-stage kidney disease. The aim of this study was to describe the characteristics and outcomes of adults with MCD and identify potential risk factors for relapse. Patients & Methods: We retrospectively studied a cohort of adults with biopsy-proven MCD in terms of clinical features and treatment outcomes. Baseline characteristics and outcomes were recorded and predictors of relapse were analyzed using logistic regression multivariate analysis. Results: 59 patients with adult-onset primary MCD with nephrotic syndrome were included. Mean serum creatinine at diagnosis was 0.8 mg/dL (±2.5) and estimated GFR (eGFR) was 87 mL/min/1.73 m2 (±29.5). Mean serum albumin was 2.5 g/dL (±0.8) and 24 h proteinuria 6.8 g (±3.7). Microscopic hematuria was detected in 35 (58.5%) patients. 42 patients received prednisone alone, six patients received prednisone plus cyclophosphamide, five patients received prednisone plus cyclosporine, one patient received prednisone plus rituximab and five patients did not receive immunosuppression at all since they achieved spontaneous remission. During a mean follow up time of 34.7(22.1) months, 46.1% of patients experienced at least one episode of relapse. The mean age of patients who did not experience a relapse was significantly higher than that of patients who relapsed while relapsers had a significantly longer duration of 24 h proteinuria prior to biopsy compared to non-relapsers. Overall, 10% of patients experienced acute kidney injury while the mean eGFR at the end was 82 mL/min/1.73 m2 (±29.1) and one patient ended up in chronic dialysis. Overall, the proportion of non-relapsers, who experienced acute kidney injury (17%) was significantly higher than the one recorded among relapsers (0%).Conclusion: In this series of patients, almost 46% of adult-onset nephrotic MCD patients experienced a relapse, although their renal progression was rare. Younger onset age was an independent risk factor for relapse in adult-onset MCD patients.

scholarly journals The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Li ◽  
Xiaoduo Fan ◽  
Xiuxia Yuan ◽  
Lijuan Pang ◽  
Shaohua Hu ◽  
...  
Keyword(s):  
Treatment Response ◽  
Butyric Acid ◽  
Serum Levels ◽  
First Episode ◽  
Healthy Controls ◽  
Significant Difference ◽  
Drug Naïve ◽  
First Episode Schizophrenia ◽  
Risperidone Treatment

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's &lt; 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's &lt; 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

Study of the HLA-DPβ1 Locus by the Polymerase Chain Reaction Technique in Patients with Hodgkin's Disease

1993 ◽  
Vol 79 (2) ◽  
pp. 133-136 ◽  
Author(s):  
Guseppe Pellegris ◽  
Claudia Lombardo ◽  
Annelisa Cantoni ◽  
Liliana Devizzi ◽  
Monica Balzarotti
Keyword(s):  
Polymerase Chain Reaction ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Polymerase Chain Reaction Method ◽  
Healthy Controls ◽  
Chain Reaction ◽  
Reaction Method ◽  
Significant Difference ◽  
Polymerase Chain

Background A number of reports have studied associations between Hodgkin's disease and HLA. Some of them established correlation between several antigens and Hodgkin's disease, and others found no correlations. Methods The HLA DP locus was determined by the polymerase chain reaction method in 31 Hodgkin's disease patients and 58 healthy controls. Results No significant difference between patients and controls was noted. Conclusions Further investigations are needed to confirm the hypothesis of a possible role of the HLA complex as one of the factors involved in Hodgkin's disease.

scholarly journals FP073PROGNOSTIC SIGNIFICANCE OF RENAL BIOPSY IN ADULT ONSET MINIMAL CHANGE DISEASE

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i73-i73
Author(s):  
Simona Stancu ◽  
Gabriel Stefan ◽  
Madalina Hoinoiu ◽  
Ioana Dicu ◽  
Cosmin Florescu ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Adult Onset

A New Cytokine-Based Stratification Is Highly Predictive of Survivals in AML Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1412-1412
Author(s):  
Pierre Peterlin ◽  
Joelle Gaschet ◽  
Thierry Guillaume ◽  
Alice Garnier ◽  
Marion Eveillard ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Risk Stratification ◽  
Univariate Analysis ◽  
Standard Of Care ◽  
Healthy Controls ◽  
First Line ◽  
Serum Samples ◽  
Gm Csf ◽  
Significant Difference ◽  
The Impact

Introduction: Recently, a significant impact of the kinetics of Fms-like tyrosine kinase 3 ligand concentration (FLc) during induction (day[D]1 to D22) has been reported on survivals in first-line acute myeloid leukemia (AML) patients (pts) (Peterlin et al, 2019). Three different FLc profiles were disclosed i) sustained increase of FLc (FLI group, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, intermediate-risk) and iii) stagnation of low levels (&lt;1000 pg/mL, FLL group, high-risk). An update of this prospective monocentric study (www.ClinicalTrials.gov NCT02693899) is presented here evaluating also retrospectively the impact on outcomes of 6 other cytokine level profiles during induction. Methods: Between 05/2016 and 01/2018, 62 AML pts at diagnosis (median age 59 yo [29-71], &lt;60 yo n=33) eligible for first intensive induction were included and provided informed consent. They received standard of care first-line chemotherapy. Serum samples collected on D1, 8, 15 & 22 of induction were frozen-stored until performing ELISA for FL, TNFa, SCF, IL-1b, IL-6, IL-10, GM-CSF. Normal values were assessed in 5 healthy controls. Pts outcomes considered were relapse/leukemia-free (LFS) and overall (OS) survivals. Results: FLI, FLD and FLL profiles were observed for 26, 22 and 14 pts respectively. A total of 372 samples were assayed for the 6 other cytokines. Median concentrations at D1, D8, D15, D22 for these 6 cytokines were as follows, considering the whole cohort (and healthy donors): TNFa: 0.53, 0, 0, 0 (0); SCF: 5.91, 0, 0, 0 (3); IL-1b : 0, 0, 0, 0 (0); IL-6: 4.85, 16.28, 10.11, 7.1 (0), IL-10: 0, 0, 0, 0 (0) and GM-CSF:1.63, 1.8, 0.67, 1.34 (9.98). Median IL-6 and GM-CSF levels, compared to healthy controls, were respectively higher and lower during induction. No significant difference was observed in terms of median cytokine concentrations at any time when comparing the three FL sub-groups or FLI vs FLD pts. With a median follow-up of 28 months (range: 17-37), FLI and FLD pts show now similar 2-y LFS (62.9% vs 59%, p=0.63) and OS (69.2% vs 63.6%, p=0.70). FLL pts have a significantly higher rate of relapse (85,7% vs FLI 19,2% vs FLD 32%, p=0,0001). Comparing FLL vs FLI+FLD pts disclosed significantly different LFS (7.1% vs 61.1%, p&lt;0.001) but not OS (36.7% vs 66.6%, p=0.11). In univariate analysis, 2y LFS and OS were not affected by the concentration (&lt; or &gt; median) of the 7 cytokines studied except for LFS and GM-CSFc at D8 (p=0,04) and D15 (p=0,08), for LFS and FLc at D1 (p=0.06), D8 (p=0,03), D15 (p=0,04) and D22 (p=0,03) and for OS and GM-CSF at D15 (p=0.08). A significant association between LFS was observed with ELN 2017 risk stratification (2-y LFS: favorable: 68,1% vs intermediate: 48,1% vs unfavorable: 30,7%, p=0.03) but not OS (2 y: 77% vs 55,5% vs 46,1%, p=0.09). Multivariate analysis showed that no factor was independently associated with OS while LFS remained significantly associated with the FLc profile (FLL vs others, HR: 5.79. 95%CI: 2.48-13.53, p&lt;0.0001) and GM-CSF at D15 (HR: 0.45; 95%CI: 0.20-0.98, p=0.04) but not with ELN 2017 risk stratification (p=0.06). Cytokine levels were then assessed to try to better discriminate FLI and FLD pts. A significant higher IL-6 level at D22 was found in relapsed or deceased FLI/FLD pts (median:15,34 vs 5,42 pg/mL, p=0,04). FLI/FLD pts with low IL-6 at D22 (&lt; median, 15.5 pg/mL, n=35 vs n=14 with high level) had significant better 2y LFS and OS (74,2% vs 38,4%, p=0,005 and 77,1% vs 38,4%, p=0,009, respectively). A new prognostic risk-stratification could thus be proposed, i.e. FLI/FLD with IL-6 &lt;15.5 pg/mL (favorable), FLI/FLD with IL-6 &gt;15.5 pg/mL (intermediate) and FLL (unfavorable). This new classification was considered for a second multivariate analysis, showing that it is the strongest factor associated with OS (p=0.006, ELN p=0.03, FL profile p=0.04) and LFS (p&lt;0.0001, ELN p=0.005, GM-CSFc D15 p=0.03) (figure 1). Conclusion: This study confirms stagnation of low FLc during AML induction as a strong poor prognosis factor. Moreover, IL-6 levels at D22 further discriminate FLI/FLD pts. Thus, a new cytokine-based risk-stratification integrating FL kinetics and IL-6 levels during induction may help to better predict outcomes in first-line AML patients. These results need to be validated on a larger cohort of AML patients while anti-IL-6 therapy should be tested in combination with standard 3+7 chemotherapy. Figure 1 Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria.

Multiplex Analysis of Serum Cytokine Levels in Waldenström Macroglobulinemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2616-2616
Author(s):  
Sherine F. Elsawa ◽  
Anne J. Novak ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
Vincent Rajkumar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Elevated Serum ◽  
Fold Increase ◽  
Serum Levels ◽  
Healthy Controls ◽  
Β2 Microglobulin ◽  
Healthy Donors ◽  
Cytokine Levels

Abstract Waldenström macroglobulinemia (WM) is a monoclonal B cell disorder characterized by a circulating monoclonal IgM protein that may lead to serum hyperviscosity in association with an infiltration of lymphoplasmacytic cells into the bone marrow. Although proinflammatory and chemotactic cytokines can profoundly affect tumor cells and the tumor microenvironment, and many cytokines have been shown to have potent therapeutic efficacy in preclinical cancer models, the role of cytokine networks in WM is not fully understood. In this study, we used a high-throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) to simultaneously test 30 cytokines, chemokines, angiogenic factors as well as growth factors and soluble receptors in the sera of WM patients and compared them with other B cell malignancies including IgM monoclonal gammopathy of undetermined significance (MGUS), follicular lymphoma, chronic lymphocytic leukemia (CLL) as well as healthy controls. Using a Mann-Whitney U test to analyze the differences between the groups, 15 of the 30 cytokines tested had significantly different levels in WM compared to healthy controls. Of those 15 cytokines, 11 were elevated in WM patients and 4 were decreased. Cytokines were grouped into 3 groups; those with &lt; 2-fold difference, 2–8 fold difference and those having &gt; 8-fold difference in their cytokine levels compared to healthy donors. There was a greater than 8-fold increase in the serum levels of Rantes, G-CSF and IL-2R (p&lt;0.0001) in WM patients. Furthermore, 3 cytokines had between 2–8-fold increase in WM patients including IL-4 (p&lt;0.0001), IL-6 (p&lt;0.0019) and IP-10 (p&lt;0.0006). Five cytokines had statistically elevated levels in WM patients compared to healthy controls, however the fold increase was &lt; 2 including HGF (p&lt;0.0185), IL-10 (p&lt;0.0002), MIP-1α (P&lt;0.0484), IL-2 (P&lt;0.0130) and IL-12 (P&lt;0.0155). Of the cytokines that had significantly lower levels in the sera of WM patients, IL-8 (p&lt;0.0001) and EGF (p&lt;0.0001) were &gt; 8-fold decreased, MCP-1 (p&lt;0.0001) was 2–8 fold lower and Eotaxin (p&lt;0.0004) was &lt; 2-fold lower in WM patients. All of the cytokines that had the greatest fold difference (&gt; 8-fold) in WM patients compared to healthy donors also differed significantly from the MGUS patients. Rantes, G-CSF, IL-2R and EGF had significantly different levels compared to other B cell malignancies. We tested for a correlation between the cytokines that had &gt; 2-fold difference between the WM group and control group with clinical features of the disease and found the cytokines IL-6 and IL-2R had a significant correlation with β2-microglobulin levels (p&lt;0.01). We analyzed cytokine levels in the bone marrow plasma of the same patients and found that high levels of IL-2R in the bone marrow microenvironment significantly correlated with anemia and elevated serum β2-microglobulin (p&lt;0.01). In conclusion, we have simultaneously analyzed sera from WM patients for 30 cytokines and found the most significantly elevated cytokines are Rantes, G-CSF and IL-2R and the most significantly downregulated cytokines are IL-8 and EGF. Furthermore, we found that elevated serum levels of IL-6 and IL-2R correlated with β2-microglobulin levels, a measure of disease activity. Further analysis of the biological role of these cytokines in WM may offer insight into disease pathogenesis and provide a basis for novel targeted therapies.

scholarly journals Glomerular glucocorticoid receptor expression is reduced in late responders to steroids in adult-onset minimal change disease

2007 ◽  
Vol 23 (1) ◽  
pp. 169-175 ◽  
Author(s):  
S. H. Han ◽  
S. Y. Park ◽  
J.-J. Li ◽  
S. J. Kwak ◽  
D. S. Jung ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Receptor Expression ◽  
Adult Onset
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