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

Author(s):  
V. Driianska ◽  
O. Petrina ◽  
M. Velychko ◽  
F. Haisenyuk ◽  
G. Drannik

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.

Author(s):  
M. Kolesnyk ◽  
G. Drannik ◽  
V. Driyanska ◽  
O. Petrina ◽  
M. Velychko

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.


Author(s):  
M. Kolesnyk ◽  
V. Driyanska ◽  
G. Drannik ◽  
O. Petrina ◽  
M. Velychko ◽  
...  

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.


2008 ◽  
Vol 7 (1) ◽  
pp. 46-50
Author(s):  
A. P. Obukhov ◽  
V. I. Prokhorenkov ◽  
L. Ye. Pospelov ◽  
Yu. V. Karacheva

have examined 133 healthy donors, 41 syphilis patients with symptoms, and 45 patients with early latent syphilis. All the examined persons were grouped by class I HLA antigens using the standard microlymphocytotoxic test. In syphilis patients, as compared to healthy persons, the frequency of HLA antigens A3, B17, and B40 was increased, while the frequency of B5 was decreased. In syphilis patients with symptoms, HLA antigens A3, B7, B17, B40 and HLA haplotypes A3B17, A3B40, A9B7 were observed with increased frequency. At the same time, in patients with early latent syphilis, HLA antigens A1, Cw3, B8, B17 and HLA haplotypes AB17, A9B8 were observed with increased frequency, while HLA antigen B5 occurred with decreased frequency. The influence of HLA antigens on occurrence of different forms of syphilis is discussed.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared


2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Danijela Tasic ◽  
Sonja Radenkovic ◽  
Gordana Kocic ◽  
Marina Deljanin Ilic ◽  
Aleksandra Ignjatovic

Aim. To determine levels of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1) in different cardiorenal syndrome (CRS) modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis.Materials and Methods. Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS.Results. C-reactive protein (CRP) was significantly higher in all CRSs in comparison to the control groupP<0.05. PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL) was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1P<0.001.Conclusions. C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable.


1981 ◽  
Vol 61 (s7) ◽  
pp. 367s-368s ◽  
Author(s):  
A. Fernandez-Cruz ◽  
M. Luque Otero ◽  
L. Llorente Perez ◽  
C. Fernandez Pinilla ◽  
N. Martell Claros

1. Human leucocyte AB antigens were determined by means of a lymphocyte toxicity test in 84 patients with essential hypertension and in 1000 blood donors. 2. The prevalence of HLA B8 was 16.4% in hypertensive patients and 8.9% in controls (P = 0.07). 3. The prevalence of HLA B12 was 34.5% in hypertensive patients and 26.9% in the control group (N.S.). In WHO stage III hypertension HLA B12 was found in six out of 10 patients. 4. The prevalence of HLA B15 was 1.2% in hypertensive patients and 6.4% in controls (P &lt; 0.05). 5. In view of a previous report of HLA antigens in a Spanish diabetic population, this study does not support the suggestion of a genetic and possibly HLA-linked connection between essential hypertension and diabetes mellitus among the Spanish population. 6. A positive family history of hypertension tended to be more common in those patients with essential hypertension associated with HLA B8.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ezzeldin Shalaby ◽  
Hisham Abdelmawgoud

Abstract Background and Aims Around worldwide population, 10% are affected by chronic kidney diseases (CKD); hemodialysis is the common choice of renal replacement therapy. Cigarette smokers have higher Lead level than non-smoker population. As Tobacco leaves are grown on polluted soil, it is proven that Mercury poisoning depends on dose and duration of exposure. Aim of the study was to determine two important toxic heavy metals elements Lead and Mercury concentrations in regular hemodialysis patients smoker and non-smoker by comparison with normal subjects and its correlation to anemia. Method Blood samples were collected from CKD patients on maintenance hemodialysis for more than 6 months divided into non-smoker and smoker to be compared with samples from a control group of non-CKD, non-smoker persons. This study was conducted in September 2019 in Al Mokattam Insurance Hospital – Cairo and involved 60 persons of both sex. They were divided into 3 groups: CKD stage 5 patients on hemodialysis 40 patients and sub-divided into 2 groups; (smoker) 20 patients and (non-smoker) 20 patients and the history of eating fish and seafood was taken. The third group was a control group included 20 healthy non-smoker participants. Lead and Mercury were analyzed by electro thermal atomic absorption spectrophotometer in Al Borg central Laboratory. The complete blood count (CBC), kidney function tests and Iron parameters were also detected. Results duration on hemodialysis did not raise Lead or Mercury level in blood, while smoking raises Lead level in blood, and eating fish and sea food more than once per week increased Mercury level in blood. There was a relation between raised Lead level and anaemia in hemodialysis patients. Conclusion Lead Prolonged and Mercury measurement is important in hemodialysis patients with possible symptoms of heavy metal toxicity. Lead level monitoring is recommended in resistant anemia in hemodialysis patients.


2005 ◽  
Vol 50 (5) ◽  
pp. 269-274 ◽  
Author(s):  
Monojit Debnath ◽  
Sujit K Das ◽  
Nirmal K Bera ◽  
Chitta R Nayak ◽  
Tapas K Chaudhuri

Objective: The etiology of delusional disorder is imperfectly understood. Involvement of biological factors has long been suspected. We examined the incidence of class I human leukocyte antigens (HLAs) in patients with delusional disorder to understand the role of HLA genes and explore a possible immunogenetic etiology for delusional disorder. Methods: We used a nested case–control study design. Psychiatric reference data were available for 27 500 patients registered between 1998 and 2003. Initially, we enrolled 150 patients with delusional disorder from the India-born Bengali population, using DSM-IV diagnostic criteria. After longitudinal follow-up, 80 patients were found to have only delusional disorder, while the remaining 70 patients represented different illnesses with paranoid symptoms and were excluded. We performed serological typing on all 150 patients and applied the polymerase chain reaction–based high-resolution molecular typing method to the 80 patients with delusional disorder. Eighty healthy donors of the same ethnic background, matched for age, sex, and other socioeconomic variables, formed the control group. Results: Some of the HLA alleles were associated with delusional disorder, and the gene HLA-A*03 was found to be significantly more frequent. This gene may influence patients' susceptibility to delusional disorder. Conclusion: The study reveals important associations between HLA genes and delusional disorder. This preliminary observation may help our understanding of this disorder's genetic basis.


Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1240-1245 ◽  
Author(s):  
DV Devine ◽  
WF Rosse

Abstract We have used the techniques of radioimmunoprecipitation (RIP) and Western blot to identify the membrane proteins that bind certain alloantibodies. Anti-PlA1 sera precipitated two bands, corresponding to platelet glycoproteins IIb and III, whether or not calcium was present during the procedure. By Western blot, this antibody bound only glycoprotein III. Anti-PlA1 serum does not precipitate proteins from the platelets of a patient with Glanzmann's thrombasthenia. Two monoclonal antibodies reacting with lymphocyte HLA antigens, as well as sera from highly allosensitized patients, precipitated bands of 38,500 and 13,500 daltons. These bands correspond to the molecular weights of the two subunits of the HLA antigen, as it has been described for other cell types. The patients' sera also precipitated a protein of 72,000 daltons from some platelets. The sera of two patients with quinidine- induced thrombocytopenia precipitated a 138,000-dalton band (glycoprotein Ib-alpha) in the presence of quinidine. The purified IgG antibody from one patient did not require other plasma factors to bind to platelets in the presence of quinidine, while purified antibody from a second patient required plasma factors other than, or in addition to von Willebrand factor. Although several sera from patients with idiopathic thrombocytopenic purpura (ITP) were tested, only one precipitated membrane proteins by the RIP method; this serum identified binding proteins corresponding to glycoproteins IIb and III.


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