scholarly journals Analysis of tissue PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels

2020 ◽  
Author(s):  
Yuemeng Sun ◽  
Ping Lan ◽  
Jie Feng ◽  
Zhigang Wang ◽  
Chao Liu ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Clinical Presentation ◽  
Remission Rate ◽  
Antigen Expression ◽  
Predominant Role ◽  
Positive Correlation ◽  
Disease Prognosis ◽  
Antibody Levels

Objective To verify serum PLA2R antibody and glomerular PLA2R antigen expression in membranous nephropathy as well as to explore their relationship with clinical presentation and disease prognosis. Methods We retrospectively analyzed 155 patients clinical figures who were diagnosed with primary membranous nephropathy by kidney biopsy. Patients were divided into 6 groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum PLA2R antibody titer. Both clinical features and pathological characteristics were recorded, and remission rate as well as time to response were compared among groups. Correlation between clinical figures and titer of PLA2R antibody or semi-quantity of PLA2R antigen were detected. Results Among patients with positive serum PLA2R antibody and tissue PLA2R antigen, higher baseline PLA2R antibody levels were associated with lower remission rate and longer remission time. A positive correlation between time to partial remission and serum PLA2R antibody titer was found. Among patients with serum PLA2R antibody titer <150U/L, there were shorter remission time in negative tissue PLA2R antigen group compared with positive tissue PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of tissue PLA2R antigen was found. Conclusion Both glomerular PLA2R antigen and serum PLA2R antibody play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum PLA2R antibody titer is less than 150U/L, while serum PLA2R antibody has predominant role in MN prognosis when serum PLA2R antibody titer is above 150 U/L.

Bactericidal antibody studies in maternal serum, colostrum, and newborn serum of the pig

1968 ◽  
Vol 14 (5) ◽  
pp. 545-550 ◽  
Author(s):  
Phyllis M. Webb ◽  
Louis H. Muschel
Keyword(s):  
Antibody Titer ◽  
Maternal Serum ◽  
Newborn Piglet ◽  
Natural Antibody ◽  
Positive Correlation ◽  
Antigenic Stimulus ◽  
Bactericidal Antibody ◽  
Antibody Levels ◽  
Serum Dependent

The development of natural bactericidal antibody levels in the piglet was studied and bactericidal antibody levels in newborn serum, maternal serum, and colostrum of the pig were determined. Natural bactericidal antibody levels in serum of the newborn piglet before ingestion of colostrum were extremely low and, as in adult serum, dependent upon natural antibody and complement for its activity. When the animals were 1 year old, large variations in natural antibody levels were found in those of a single litter. The levels of natural antibody in maternal serum, colostrum, and precolostral newborn serum did not reveal a positive correlation. Finally, immunization of gilts before delivery provided a very effective antigenic stimulus in the piglets whose antibody titer, when the animals were 2 weeks old, was comparable to that of the immunized parent.

A Comparative Study of the Gut Microbiota Associated with Immunoglobulin A Nephropathy and Membranous Nephropathy

2020 ◽  
Author(s):  
shiren sun ◽  
Ruijuan Dong ◽  
Ming Bai ◽  
Jin Zhao ◽  
Di Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Amplicon Sequencing ◽  
Healthy Controls ◽  
Immunoglobulin A Nephropathy ◽  
Positive Correlation ◽  
16S Rdna Amplicon Sequencing ◽  
The Oxford Classification

Abstract Background The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN versus healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). Results The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Fusobacterium . Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis , Streptococcus, and Enterobacteriaceae_ unclassified increased, while that of Lachnospira, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella , Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Conclusions Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

P0433AGE-RELATED DIFFERENCES IN THE SPECTRUM OF BIOPSY-PROVEN GLOMERULONEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina-Stela Capusa ◽  
Nicolae Pana ◽  
Otilia Popa ◽  
Laura Chiotan ◽  
Eugen Mandache ◽  
...  
Keyword(s):  
Young Adults ◽  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Clinical Presentation ◽  
The Elderly ◽  
Very Elderly ◽  
Age Related ◽  
Nephritic Syndrome ◽  
Thin Basement Membrane Disease

Abstract Background and Aims The proportion of geriatric population is increasing globally and age-related changes, as kidney ageing and decline in immunocompetence, might interfere with frequency of various glomerulopathies (GP). Thus, it is conceivable that the spectrum of biopsy-proven GP varies across different age categories. Accordingly, we aimed to describe age-related variation in clinical presentation and the in prevalence of GP diagnosed by kidney biopsy (KB) in adults. Method This retrospective study enrolled 1254 subjects selected from the KB database of a large tertiary academic Nephrology center (which provides specialized care for the south-eastern part of our country), over a ten-year span (01.01.2008-31.12.2017). Inclusion criteria were age &gt;18 years, native kidney biopsy, availability of data from light, immunofluorescence, and electron microscopy, and a histologic diagnosis of GP. Repeated biopsies and inadequate tissue samples were excluded. Demographic (age, gender), clinical and laboratory data at the time of biopsy were extracted from medical records for all the selected subjects. To investigate the possible influence of age on the spectrum of biopsy-proven GP, the cohort was divided into 4 categories: young adults (18 to 30 years, n=156), adults (31 to 64 years, n=868), elderly (65 to 74 years, n=176) and very elderly (≥75 years, n=54), and the collected data were compared by non-parametric methods (Mann-Whitney, Chi2 and Fisher exact tests). Results The nephrotic syndrome was the most common presentation form in all age groups but had a higher prevalence in very elderly (62%) and elderly (55%) as compared to adults (37%, p=0.01) and young adults (41%, p&lt;0.001). In the groups below age of 65, the chronic nephritic syndrome was the second most common indication for KB (31% and 28%, respectively), followed by chronic renal failure in adults (13%) and acute nephritic syndrome in young adults (10%). Lupus nephritis (LN) and IgA nephropathy (IgAN) were the most commonly diagnosed GP in young adults (22% each), followed by minimal change disease (MCD, 14%), membranous nephropathy (MN, 8%), focal and segmental glomerulosclerosis (FSGS, 8%), and thin basement membrane disease (6%). In adults, the most common GP were: IgAN (23%), MN (15%), diabetic nephropathy (DN, 11%) and MCD (10 %). Conversely, in both the elderly and the very elderly, the most common biopsy-proven GP was MN (26% each). Elderly had renal amyloidosis as the second most prevalent histological diagnosis (17%), followed by DN (11%), and by IgAN and MCD (≈10% each). Crescentic glomerulonephritis (CGN) occurred in 7.5% of the elderly, but it was the second pathology (17%) in subjects aged 75+ years, followed by MCD (15%) and DN (13%). IgAN and amyloidosis were identified in about 5% of this group. It appears that the prevalence of both clinical presentation and histologically diagnosed GP showed some similarities between the first two and, respectively, last two age categories. Conclusion Biopsy-proven GP have different frequencies depending on the patient’s age, with some pathologies predominantly found at older ages (such as membranous nephropathy, amyloidosis and crescentic GN) or, on the contrary, typical for young adults (lupus nephritis and IgAN). These differences account for the distinct clinical presentations at the time of KB.

scholarly journals Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linda Reinhard ◽  
Cindy Thomas ◽  
Maya Machalitza ◽  
Erik Lattwein ◽  
Lothar S. Weiss ◽  
...  
Keyword(s):  
Western Blot ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Reducing Conditions ◽  
Igg3 Subclass ◽  
Antibody Levels ◽  
First Time

AbstractMembranous nephropathy (MN) is an autoimmune disease caused by autoantibodies against the podocyte antigens phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing protein 7A (THSD7A) in 80% and 2–3% of patients, respectively. THSD7A antibodies are considered to be pathogenic and highly specific for MN patients. Using an indirect immunofluorescence test (IIFT) we detected THSD7A-antibodies (titre 1:10) in the serum of a patient with high proteinuria who, however, in the kidney biopsy was diagnosed with diabetic nephropathy and MN was excluded as a possible cause of proteinuria. Different immunofluorescence assays and Western blot techniques using recombinant THSD7A (rTHSD7A) or THSD7A from different human tissues revealed that the circulating THSD7A-autoantibodies were only of the IgG3 subclass. The patient serum reacted exclusively with rTHSD7A and only when the antigen was present in reducing Western blot conditions, or on formaldehyde-fixed cells for the IIFT. Our findings show for the first time the existence of circulating THSD7A-antibodies recognizing denatured/reduced rTHSD7A, which do not react with glomerular THSD7A in vivo and are thus presumptively non-pathogenic. As a consequence, kidney biopsy or Western blot analyses of THSD7A under non-reducing conditions should be performed to confirm the diagnosis of THSD7A-associated MN, especially in cases with low THSD7A-antibody levels in the IIFT.

scholarly journals Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy

2019 ◽  
Vol 31 (1) ◽  
pp. 197-207 ◽  
Author(s):  
Linda Reinhard ◽  
Gunther Zahner ◽  
Stephan Menzel ◽  
Friedrich Koch-Nolte ◽  
Rolf A.K. Stahl ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Epitope Spreading ◽  
Clinical Role ◽  
Epitope Region ◽  
Epitope Recognition ◽  
Domain Specific ◽  
Disease Prognosis ◽  
Phospholipase A2 Receptor ◽  
Antibody Levels

BackgroundAntibodies against phospholipase A2 receptor 1 (PLA2R1) are found in 80% of patients with membranous nephropathy, and previous studies described three autoantibody-targeted PLA2R1 epitope regions. Although anti-PLA2R1 antibody levels are closely associated with treatment response and disease prognosis, the clinical role of epitope regions targeted by autoantibodies is unclear.MethodsIn a prospective cohort of 150 patients with newly diagnosed PLA2R1-associated membranous nephropathy, we investigated the clinical role of epitope-recognition patterns and domain-specific PLA2R1 antibody levels by western blot and ELISA.ResultsWe identified a fourth epitope region in the CTLD8 domain of PLA2R1, which was recognized by anti-PLA2R1 antibodies in 24 (16.0%) patients. In all study patients, anti-PLA2R1 antibodies bound both the N-terminal (CysR-FnII-CTLD1) region and the C-terminal (CTLD7-CTLD8) region of PLA2R1 at study enrollment. The total anti-PLA2R1 antibody levels of patients determined detection of domain-specific PLA2R1 antibodies, and thereby epitope-recognition patterns. A remission of proteinuria occurred in 133 (89%) patients and was not dependent on the domain-recognition profiles. A newly developed ELISA showed that domain-specific PLA2R1 antibody levels targeting CysR, CTLD1, and CTLD7 strongly correlate with the total anti-PLA2R1 antibody level (Spearman’s rho, 0.95, 0.64, and 0.40; P<0.001, P<0.001, and P=0.002, respectively) but do not predict disease outcome independently of total anti-PLA2R1 antibody levels.ConclusionsAll patients with PLA2R1-associated membranous nephropathy recognize at least two epitope regions in the N- and C-terminals of PLA2R1 at diagnosis, contradicting the hypothesis that PLA2R1 “epitope spreading” determines the prognosis of membranous nephropathy. Total anti-PLA2R1 antibody levels, but not the epitope-recognition profiles at the time of diagnosis, are relevant for the clinical outcome of patients with this disease.

scholarly journals Mechanisms of Primary Membranous Nephropathy

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 513
Author(s):  
Yan Gu ◽  
Hui Xu ◽  
Damu Tang
Keyword(s):  
Membranous Nephropathy ◽  
Full Spectrum ◽  
The Past ◽  
Phospholipase A2 Receptor ◽  
Kidney Glomerulus ◽  
Recent Developments ◽  
One Step ◽  
Stage Renal Disease ◽  
End Stage ◽  
Antibody Levels

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50–80% and 3–5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5–10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.

Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease

2018 ◽  
Vol 36 (5) ◽  
pp. 369-376 ◽  
Author(s):  
Nurit Loberman-Nachum ◽  
Michael Schvimer ◽  
Camila Avivi ◽  
Iris Barshack ◽  
Avishay Lahad ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Immunohistochemical Staining ◽  
Clinical Presentation ◽  
Tissue Transglutaminase ◽  
Mucosal Damage ◽  
High Serum ◽  
Tissue Transglutaminase Antibodies ◽  
Antibody Levels ◽  
Age Range ◽  
Multiple Symptoms

Background: The clinical, histological, and serological spectrum of celiac disease (CD) vary widely. We aimed to examine relationships between symptoms, serum anti-tissue transglutaminase antibodies (tTG) levels, mucosal damage, and mucosal anti-tTG deposits in pediatric CD. Methods: A retrospective single-center, cohort study of children referred for endoscopy with suspected CD during 2011–2014. We retrieved the clinical data, blindly reviewed duodenal biopsies, and performed immunohistochemical staining for anti-tTG deposits. Patients were classified as monosymptomatic or polysymptomatic. Mucosal anti-tTG deposits were classified according to the location of deposits, dominant intensity, maximal intensity, and percentage of stained area. Results: Of 252 patients with confirmed CD, complete data were available for 100: 37 males in the age range 1.3–16.7 with median 4.0 years. Monosymptomatic patients (n = 54) presented at an older age than polysymptomatic patients (1.3–15.5, median 8.1 vs. 1.3–16.7, median 6.3 years, p = 0.026). Marsh 2–3c was more prevalent in polysymptomatic patients (93 vs. 78%, p = 0.028). The intensity of mucosal anti-tTG deposits correlated with serum anti-tTG levels but not with the clinical presentation. Conclusions: Multiple symptoms and high serum anti-tTG antibody levels correlated with mucosal damage in children with CD. The role of immunohistochemical staining for intestinal anti-tTG mucosal deposits in the diagnosis of borderline CD is not yet established.

scholarly journals Management Problems in Global Crowdsourcing

2022 ◽  
Vol 30 (3) ◽  
pp. 1-15
Author(s):  
Zhijiang Liu ◽  
Tatyana Sakulyeva ◽  
Alexey Mikheev ◽  
Diana Stepanova
Keyword(s):  
Intellectual Property ◽  
Property Rights ◽  
Intellectual Property Rights ◽  
Project Success ◽  
Information Leakage ◽  
Ethical Conduct ◽  
Predominant Role ◽  
Positive Correlation ◽  
Security Guarantees

The study aimed to develop recommendations for the optimization of settings in which the crowdsourcing project takes place. Findings show that crowdfunding projects are hybrid and include the elements of crowdsourcing, crowdsensing, crowdfunding, crowdworking, and crowdsourced recruitment. The predominant role of security guarantees was identified. It turned out that relations irreducible to a simple hierarchy pose many challenges. The results indicate that leading issues include the lack of financial guarantees and the likelihood of information leakage to competitors. Hence, the priority is to manage the exchange of money and information. An interesting finding demonstrates a positive correlation between project success, ethical conduct, and fair distribution of gains. The protection of intellectual property rights was no less important. As it was concluded in the course of analysis, the more successful the project, the more thoroughly it addresses the protection of someone else's intellectual property.

scholarly journals Aberrant Antigen Expression in Children with Acute Leukemia A Flow Cytometric Analysis

2018 ◽  
Vol 12 (1) ◽  
pp. 10-14
Author(s):  
Nusrat Jahan ◽  
Humayun Sattar ◽  
Shirin Tarafder ◽  
Chandan Kumar Roy ◽  
Irin Rahman ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Remission Rate ◽  
Flow Cytometric Analysis ◽  
Antigen Expression ◽  
Prognostic Indicator ◽  
High Risk Group ◽  
Protein Markers ◽  
Clinical Tool ◽  
Acute Leukemias ◽  
Childhood Acute Leukemia

The primary clinical tool for predicting the lineage potential of leukemic blasts is the characterization of protein expression by immunophenotyping. It is common for acute leukemias to aberrantly express protein markers more typically associated with other lineages. Therefore, this study was designed to assess the frequency of aberrant antigens expression in childhood acute leukemia. Peripheral blood and bone marrow samples were collected from 76 clinically suspected and morphologically diagnosed untreated cases of acute leukemia (children of 0-<18 years). Flow cytometry immunophenotyping was carried out with the help of Flow cytometer (BD FACSVerse). Total 9 (11.84%) cases showed aberrant antigens expression. Out of 9 aberrantly expressed cases, 2 (22.22%) AML cases showed aberrant lymphoid marker CD7 expression. Co-expression of myeloid markers CD13 and CD117 found in 2 (22.22%) B-ALL cases and 2 (22.22%) cases of B-ALL expressed myeloid marker CD117. Myeloid marker CD33 expressed by 2 (22.22%) case of B-ALL. Only 1(11.11%) T-ALL case co expressed myeloid markers CD33 and CD117. These findings may help to recognize patients with high risk group and low remission rate as aberrant antigen expression may represent a poor prognostic indicator. Further studies are needed to confirm the correlation between aberrant phenotypes with prognosis and therapeutic response of acute leukemia. Bangladesh J Med Microbiol 2018; 12 (1): 10-14

HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy

2021 ◽  
pp. CJN.18021120
Author(s):  
Wei-Bo Le ◽  
Jingsong Shi ◽  
Fan Yang ◽  
Si-Wen Gong
Keyword(s):  
Membranous Nephropathy ◽  
Prospective Cohort ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Chinese Patients ◽  
Hla Alleles ◽  
Cox Analysis ◽  
Antibody Levels ◽  
Egfr Decline

Background and objectives Associations between HLA alleles and susceptibility to PLA2R-related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear. Design, setting, participants, & measurements Five HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied. Results A total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 (n=12, HR 3.7, 95% CI 1.8 - 7.8, P < 0.001) , DQB1*06:03 (n=12, HR 3.7, 95% CI 1.8 - 7.8, P < 0.001), DRB1*04:05 (n=12, HR 3.8，95% CI 1.5 - 9.5, P = 0.004) and DQB1*03:02 (n=21, HR 3.1，95% CI 1.4 - 6.7, P = 0.005), were associated with a ≥ 40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥ 40% eGFR decline during follow-up (HR 3.9, 95% CI 2.3 - 6.7, P < 0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (HR 4.1, 95% CI 2.3 - 7.1, P < 0.001). Conclusions Carrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05 and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.

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