scholarly journals ASSOTIATIONS OF PECULIARITIES OF HLA-PHENOTYPE AND THE SENSIBILITY TO THE CORTICOSTEROID TREATMENT IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS WITH NEPHROTIC SYNDROME

2017 ◽  
pp. 37-44
Author(s):  
M. Kolesnyk ◽  
G. Drannik ◽  
V. Driyanska ◽  
O. Petrina ◽  
M. Velychko
Keyword(s):  
Nephrotic Syndrome ◽  
Hla Antigens ◽  
Corticosteroid Treatment ◽  
Steroid Resistance ◽  
Control Group ◽  
Chronic Glomerulonephritis ◽  
Healthy Donors ◽  
Steroid Sensitive ◽  
Steroid Sensitivity ◽  
Hla Phenotype

The purpose of study was determination of HLA -antigens I and II classes as predictors of ineffectiveness of initial steroid therapy, and according prognozonegative markers of chronic glomerulonephritis with nephrotic syndrome. Methods. In 59 chronic glomerulonephritis with nephrotic syndrome patients (steroid sensitive n=33 (1 gr.) and steroid resistant’s n= 26 (2 gr.)) and 350 healthy donors( control group) studied HLA antigens I and II classes of the special anti- HLA-antigens panel (20 antigens of locus A, 31 – of locus B and 9- of locus DR). Result. In patients with chronic glomerulonephritis, nephrotic syndrome with hormone sensitivity relative risk is high at the presents of A28 (RR=8,5, r р <0,001), it made attributive risk (=0,37). In comparison with a control group, RR>2 for antigens  A11  (RR=2,23), A23 (RR=4,28),  A24 (RR=3,3),  A29 (RR=10,78) that A30 (RR=11,23); attributive risk more than 0,1 for the antigen A11 (=0,16) ; A24 (=0,13), other did not differ from control. Subzero connection is exposed for the antigens of A2 (р<0,001), А9 (р=0,007). In locus antigen B14 (RR=5,65, р =0,001) are exposed, B44 (RR=48,25, р =0,004), B51(RR=12,32, р =0,006) and attributive risk of development of disease (according =0,24, 0,12 ; 0,14); and antigens B38 and B41 (RR=11,57, р=0,05). The steroid sensitivity was associated with the antigens B5 (p=0,033), B12 (p=0,005) and B35 (p=0,021). In locus DR made etiologic faction antigens DR4 (RR=7,0 and =0,24) DRw52 (RR=7,0 and =0,25). Conclusions. For patients with chronic glomerulonephritis with a nephrotic syndrome antigens of HLA-B14,B38, B51, DRw52 are associated with steroid sensitivity. The attributive risk of steroid resistance is high for split A19+31+32, antigens B8, B55.

scholarly journals Peculiarities of phenotypes of patients with pyelo- and glomerulonephritis by HLA distribution analysis

2018 ◽  
pp. 11-18
Author(s):  
V. Driianska ◽  
O. Petrina ◽  
M. Velychko ◽  
F. Haisenyuk ◽  
G. Drannik
Keyword(s):  
Kidney Diseases ◽  
Hla Antigens ◽  
Causal Role ◽  
Control Group ◽  
Distribution Analysis ◽  
Immune Disorder ◽  
Hla Antigen ◽  
Healthy Donors ◽  
Hla Phenotype ◽  
High Production

Studies devoted to the role of human leucocyte antigens (HLA) in pathogenesis of chronic kidney disease (CKD) have demonstrated the associative links of the HLA antigens, which stipulate the relative and attributive risks of some autoimmune diseases, with immune disorder and a high production of pro-inflammatory cytokines. The aim of our study was to determine the peculiarities of phenotypes of CKD patients according to the distribution of HLA-A, B and DR antigens and to conduct their comparative analysis in patients with pyelonephritis (PN) and glomerulonephritis (GN). Methods: The distribution of HLA-A, B, DR antigens in 384 CKD patients (120 with PN and 264 with GN) was analyzed. HLA antigens were defined using a standard microlymphocytotoxic test on the Terasakiґs planchette with special panels of anti-HLA serums (20 antigens of locus A, 31 – B and 9 – DR). The control group consisted of 350 healthy donors. The HLA antigen frequencies in normal and diseased subjects were compared taking each antigen separately, using χ2 test. The etiologic fraction (attributive risk s > 0,1) was counted using the formula: s = x - y/I- y, where x is frequency of antigen in patients and y is frequency in healthy. The s  reading was considered reliable when it exceeded 0.1. Results. The causal role (σ > 0,1) was determined for А10, А11; В14, В16 for PN; antigens-protectors - А2, В21, В35, В40. For CGN, NS the relative risk is high (RR > 2) at the presence of HLA-A23, А24, А28; B8, В38, В41, В44; DR1, DR4, DRw52 in phenotype, the causal role in etiopathology (σ>0.1) is indicated for A24,А28; B8; DR1, DR4, DRw52; the disease protectors are B12 and B16. Conclusion. Conclusion. The features of the HLA-phenotype of patients with pyelo- and glomerulonephritis were shown. It allowed to establish the interconnectedness of the antigens of the histocompatibility complex with the risk of kidney diseases developing, which could help to personificate of the treatment and predicte of the course of the disease.

scholarly journals ASSOCIATION OF HLA AND CYTOKINES OF BLOOD WITH ANTIINFLAMMATORY EFFECTS IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS

2017 ◽  
pp. 13-19
Author(s):  
M. Kolesnyk ◽  
V. Driyanska ◽  
G. Drannik ◽  
O. Petrina ◽  
M. Velychko ◽  
...  
Keyword(s):  
Serum Level ◽  
Prognostic Markers ◽  
Hla Antigens ◽  
Serum Levels ◽  
High Serum ◽  
Chronic Glomerulonephritis ◽  
Healthy Donors ◽  
Lower Serum Level ◽  
Steroid Sensitive ◽  
Antiinflammatory Effects

Cytokines and HLA take important part in immunogenesis of many diseases, therefore the analysis of these indices and this associations in dependence of glomerulonephritis (GN) can define their value as the additional prognostic markers. Aim of the work is to determine the of associations the high serum levels of cytokines (IL-4, IL-17) and peculiarities of some HLA in phenotype to substantiate of chronic glomerulonephritis with nephrotic syndrome (CGN, NS) immunogen- esis and to ascertain the additional prognostic markers. Materials and methods. There was studied the HLA-antigens distribution in the 264 adult patients CGN, NS (the diagnosis was confirmed morphologically using the thin needle nephrobiopsy) and 350 healthy donors by typing the lymphocytes with the aid of standard microlymphocytotoxic test (Terasaki’s test). HLA antigens were defined using a standard microlymphocytotoxic test on the Terasaki's planchette with special panels ofanti-HLA serums (20 antigens of locus A, 31 - B and 9 - DR). The etiologic fraction (attributive risks ) was counted using the formula: ct = x - y/I - y, where x - frequency of antigen in patients and y - frequency in healthy. The ct reading was considered significant when it exceeded 0,1. Using ELISA, the level of the cytokines was studied in the blood serum - IL-4 in 76 and IL-17 – 79 patients. Results. HLA-A23, -24, -28, -B8, -38, -41, -44, DR1, -4, -w52 in adults patients have associations (RR>2) CGN, NS; the attributive risk (AR) (<j>0,1) to develop GN detected in patients have A24, A28, B8, DR 1, 4, w52. The CGN, NS patients has statistically higher serum level of the IL-4 and IL-17, with more high indices of this cytokines in patients with attributive risk antigens HLA-A24 and A-28. The highest levels of IL-17 detected also in adults case have B14 and B38, which associated with steroid sensitive NS. HLA-B8, which associated with steroid resistant NS, have more patients with CGN, NS with lower serum level of antiinflammatory IL-4. Conclusion. The patients with CGN, NS have associations of HLA and serum levels of pro- and antiinflammatory cytokines IL-4 and IL-17, which play role of additional prognostic predictors.

scholarly journals Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

2021 ◽  
pp. 32-37
Author(s):  
Ie. A. Burlaka ◽  
I. V. Bagdasarova
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Control Group ◽  
Activation Markers ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Cellular Hypoxia ◽  
Steroid Sensitive ◽  
Nephrotic Children

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome. Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need. Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study. Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children. 

scholarly journals HLA-PHENOTYPE IN PATIENTS WITH GLOMERULONEPHRITIS WITH VARIOUS MORPHOLOGIC FORMS AND NEPHROTIC SYNDROM

2016 ◽  
pp. 36-44
Author(s):  
M. Kolesnyk ◽  
V. Driyanska ◽  
G. Drannik ◽  
O. Petrina ◽  
M. Velychko ◽  
...  
Keyword(s):  
Renal Failure ◽  
Prognostic Markers ◽  
Hla Antigens ◽  
Chronic Glomerulonephritis ◽  
Hormone Resistance ◽  
Disease Course ◽  
Etiologic Role ◽  
Healthy Donors ◽  
Hla Phenotype

In the work was determined the HLA-phenotype specificities in patients with different morphologic forms of chronic glomerulonephritis and nephrotic syndrome (CGN, NS) to define the additional predictors of a disease course. Materials and methods. There was studied the HLA-antigens distribution in the 264 CGN, NS patients and 350 healthy donors by typing the lymphocytes with the aid ofstandard microlymphocytotoxic test (Terasaki’s test). The diagnosis was confirmed morphologically using the thin needle nephrobiopsy. Results. It is advisable to associate CGN, NS (RR > 2) with antigens HLA- A23, 24, 28; B8, 38, 41, 44 in patients; the causal role (a > 0.1) was determined for A24, 28; B8. In proliferative GN was additionally revealed the etiologic role of B27 known as antigen associated with risk ofautoimmune diseases. In patients with various morphologic forms is advisable the association of some antigens with development of chronic renal failure (CRF) – A30, B41 in FSGS, A10 – MGN; and also hormone resistance (HR) – A19+31+32 in FSGS, B8 – MGN and MC. Conclusion. The revealed reliable associations ofHLA types both with CGN, NS and its separate morphologic forms with the risk of CRF and/or HR allow take into consideration the availability ofsuch antigens in phenotype ofpatients with confirmed by biopsy diagnosis as the additional diagnostic and prognostic markers.

scholarly journals ASSOCIATION OF HLA AND PROINFLAMMATORY CYTOKINES OF BLOOD IN PATIENTS WITH GLOMERULONEPHRITIS

2017 ◽  
pp. 35-41 ◽  
Author(s):  
M. Kolesnyk ◽  
V. Driyanska ◽  
M. Velychko ◽  
G. Drannik ◽  
O. Petrina
Keyword(s):  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Proinflammatory Cytokines ◽  
Prognostic Markers ◽  
Hla Antigens ◽  
Serum Levels ◽  
High Serum ◽  
Chronic Glomerulonephritis ◽  
Healthy Donors ◽  
Negative Marker

Introduction. Cytokines and HLA are of important part of immunogenesis of many diseases, therefore the analysis of these indices and this associations in dependence of glomerulonephritis (GN) can define their value as the additional prognostic markers. Aim of the work is to determine the peculiarities of associations the high serum levels ofproinflammatory cytokines (TNF a, MCP-1, IL-18) and some HLA in phenotype to substantiate of chronic glomerulonephritis with nephrotic syndrome (CGN, NS) immunogenesis and to ascertain the additional prognostic markers. Materials and methods. There was studied the HLA-antigens distribution in the 264 CGN, NS adult patients and 350 healthy donors by typing the lymphocytes with the aid of standard microlymphocytotoxic test (Terasaki’s test). Using IFA, the level of the proinflammatory cytokines was studied in the blood serum - MCP-1 in 39, IL-18 – 40 and TNF-a - 96patients. Results. HLA-A23, -24, -B8, -38, -41, -44, DR1, -4, -w52 in adults patients have associations (RR>2) CGN, NS; the attributive risk (a>0,1) to develop GN detected in patients have A24, B8, DR 1, 4, w52. The relative risk (RR) to develop chronic renal failure (CRF) is in detection of HLA-10, -29, -30, -41, -51, DR4; attributive risk (AR) - A10. The CGN, NS patients showed statistically higher level of the serum proinflammatory cytokines – TNF-6, IL-17, MCP-1 with more high indices of the TNF-a in patients with HLA-A23, -A28, -B44 (RR of CGN, NS), -A10 (AR of CRF), IL-18 - A24 (AR of CGN, NS) ma A10 (AR of CRF). The highest levels of MCP-1 detected in adults case have risk antigens - relative B41, attributive - A28, B8, and predictor of CRF B41, wich may be negative marker for prognosis. Conclusion. It was to determine associations the serum levels of some cytokines and HLA in patients with CGN, NS. We think it appropriate to study HLA and proinflammatory cytokines TNF-a, IL-18 and MCP-1 in blood as additional negative prognostic predictors for the differentiating approach to treatment.

Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children

2014 ◽  
Vol 30 (2) ◽  
pp. 301-307 ◽  
Author(s):  
Zhaoyang Peng ◽  
Jianhua Mao ◽  
Xuejun Chen ◽  
Fengqing Cai ◽  
Weizhong Gu ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

scholarly journals Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

2019 ◽  
Vol 5 (2) ◽  
pp. e15-e15
Author(s):  
Mohsen Akhavan Sepahi ◽  
Najmeh Farahani ◽  
Mohammad Reza Razavi ◽  
Hossein Heydari ◽  
Shahram Arsang-Jang
Keyword(s):  
Clinical Trial ◽  
Nephrotic Syndrome ◽  
Intervention Group ◽  
T Test ◽  
Steroid Resistance ◽  
Control Group ◽  
Steroid Resistant ◽  
Steroid Administration ◽  
Frequent Relapses ◽  
The Mean

Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P<0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P<0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P<0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

scholarly journals SOCS3 is epigenetically up-regulated in steroid resistant nephrotic children.

2016 ◽  
Vol 63 (1) ◽  
Author(s):  
Katarzyna Zaorska ◽  
Piotr Zawierucha ◽  
Danuta Ostalska-Nowicka ◽  
Michał Nowicki
Keyword(s):  
Nephrotic Syndrome ◽  
Methylation Status ◽  
Study Groups ◽  
Epigenetic Mechanism ◽  
Steroid Resistance ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Steroid Resistant ◽  
Steroid Sensitive ◽  
Nephrotic Children

The mechanism of steroid resistance in children with the nephrotic syndrome is yet unknown. About 20% of patients demonstrate steroid unresponsiveness and progress to end stage renal disease. Aberrant SOCS3 and SOCS5 expression in steroid resistant and sensitive patients has previously been demonstrated. Here, we investigate genetic and epigenetic mechanisms of regulation of SOCS3 and SOCS5 transcription in nephrotic children. 76 patients with the nephrotic syndrome (40 steroid resistant and 36 steroid sensitive) and 33 matched controls were included in this study. We performed genotyping of a total of 34 single nucleotide polymorphisms for SOCS3 and SOCS5 promoters and evaluated their methylation status using MS-PCR and QMSP methods. Steroid resistant patients had a significantly lower methylation of one region of SOCS3 promoter in comparison with steroid sensitive patients and controls (p < 0.0001). However, the relative methylation level in the steroid sensitive patients and controls differed significantly even before the first steroid dose (p = 0.001758). Other SOCS3 and SOCS5 promoter regions displayed no differences in methylation or were fully methylated/unmethylated in all study groups, showing site-specific methylation. The allele and genotype distribution for SOCS3 and SOCS5 markers did not differ statistically between the groups. We demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients.

scholarly journals The role of cell signaling molecules in the pathogenesis of glomerulonephritis in children

2021 ◽  
Vol 64 (2) ◽  
pp. 37-41
Author(s):  
Angela Ciuntu ◽  
Keyword(s):  
Nephrotic Syndrome ◽  
Cell Signaling ◽  
Clinical Manifestations ◽  
Signaling Molecules ◽  
Control Group ◽  
Healthy Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Background: Cytokines are functional class of tiny proteins and glycoprotein and fundamentally they are monomers that function as soluble mediators in an autocrine or paracrine manner. Cytokines are produced by a number of cell types, predominantly leukocytes, and their targets implicate both immune and non-immune cells. Material and methods: This study was performed on 75 children with glomerulonephritis (GN), aged from 2 up to 17 years. There were 20 children with steroid-sensitive nephrotic syndrome (SSNS), 15 children with steroid-resistant nephrotic syndrome (SRNS), 20 children with chronic glomerulonephritis (CGN) nephrotic form and 20 children with CGN mixed form. This study was performed on patients experiencing disease relapse and clinical remission. The control group consisted of 20 healthy children. Results: The results of this study demonstrated increased levels of cell signaling molecules (IL-8, TNF-α, MCP-1, MIP-1α) in the urine during clinical manifestations, valuable result due to their major role in the immunopathogenic mechanism of proteinuria in nephrotic syndrome. Conclusions: Determination of urinary concentrations of cellular signaling molecules may be useful as a predictive non-invasive method for estimating disease activity, monitoring disease progression, differentiating steroid-sensitive nephrotic syndrome from steroid-resistant nephrotic syndrome, and assessing the effectiveness of treatment in children with different variants of GN

scholarly journals HLA-B60 and HLA-DR4 alleles in Javanese children with steroid-sensitive primary nephrotic syndrome

2016 ◽  
Vol 46 (6) ◽  
pp. 246
Author(s):  
M P Damanik
Keyword(s):  
Nephrotic Syndrome ◽  
Strong Association ◽  
Control Sample ◽  
Hla Class I ◽  
Control Group ◽  
Healthy Children ◽  
Primary Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Sequence Specific Oligonucleotide Probe

Background Steroid-sensitive nephrotic syndrome (SSNS) ofchildren is associated with several human leucocyte antigen (HLA)class I and class II.Objective To investigate the association between HLA-B60 andHLA-DR4 alleles and primary nephrotic syndrome (PNS) inJavanese children.Methods A case control study was conducted on 47 Javanesechildren with PNS who were typed for HLA-B60 and HLA-DR4 al-leles, using DNA sequence specific oligonucleotide probe (SSOP)as control sample, 47 healthy children were also typed for thoseHLA antigens using the same technique.Results Compared with control group, children with PNS had higherfrequency of both HLA-B60 (23.32% vs 4.3%; OR=6.85 [CI=1.32-35.65]; P<0.01) and HLA-DR4 (40.0% vs 2.1%; OR=30.67 [CI:3.71-253.33]; P<0.0002). There was association between HLA and PNSwith SSNS in children.Conclusion The strong association between PNS and HLA anti-gen support the immunogenetic background of the disease, whichseems to be stronger in young children with SSNS.

Sign in / Sign up

Export Citation Format

Share Document