scholarly journals Circulating CD14+CD163+CD206+ M2 Monocytes Are Increased in Patients with Early Stage of Idiopathic Membranous Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Hou ◽  
Manli Zhang ◽  
Yuhong Ding ◽  
Xinrui Wang ◽  
Tao Li ◽  
...  

Aim. To analyze changes in peripheral blood monocytes and their clinical significance in patients with early stage of idiopathic membranous nephropathy (IMN). Methods. A total of 27 patients with early stage of IMN and 16 age- and sex-matched healthy controls (HCs) were recruited for the study. The monocyte subset counts in circulation were measured by flow cytometry, and serum interleukin- (IL-) 10 and IL-12 concentrations were tested by enzyme-linked immunosorbent assay. The potential association between clinical signs and monocyte subset counts was analyzed statistically. Results. Compared with the HCs, the patients with early stage of IMN had higher counts of CD14+CD163+, CD14+CD163+CD206+, and CD14+CD163+CD206+CD115+ M2-like monocytes. The CD14+CD163+CD206+ M2-like cell counts and intracellular IL-10 concentrations in the monocytes were positively correlated with progression in proteinuria. The levels of serum IL-10 were significantly higher in early IMN patients than in the HCs. Furthermore, CD14+CD163+CD206+ M2-like cell counts in the patients with incipient IMN were also positively related with 24 h urinary albumin levels and the values of serum M-type phospholipase A2 receptor (PLA2R). Conclusion. CD14+CD163+CD206+ M2-like monocytes may contribute to the pathologic process in early-stage IMN and could serve as potential markers for evaluating the disease severity.

2019 ◽  
Vol 34 (4) ◽  
pp. 406-413
Author(s):  
Dan Zhang ◽  
Chong Zhang ◽  
Fan Bian ◽  
Wenzhu Zhang ◽  
Gengru Jiang ◽  
...  

Background: Membranous nephropathy is the most common glomerular disease related to malignancy. However, it is difficult to distinguish between true malignancy-related membranous nephropathy and idiopathic membranous nephropathy coincident with cancer. It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy. Therefore, the aim of this study was to compare the clinicopathological characteristics between membranous nephropathy patients with cancer and idiopathic membranous nephropathy patients without cancer to better detect malignancy-related membranous nephropathy, including glomerular PLA2R and THSD7A depositions and their circulating antibodies, together with glomerular IgG4 deposition. Methods: Twelve membranous nephropathy patients with cancer and 257 idiopathic membranous nephropathy patients without cancer were included in this study and had been followed up for more than 1 year. The glomerular expression of PLA2R, THSD7A, and IgG4 was analyzed by immunohistochemistry. Circulating anti-PLA2R and anti-THSD7A antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence testing, respectively. Results: Membranous nephropathy patients with cancer were significantly older and had higher serum creatinine and a lower estimated glomerular filtration rate than idiopathic membranous nephropathy patients ( P<0.05). The positive rates of glomerular PLA2R and IgG4 depositions and circulating anti-PLA2R antibodies in membranous nephropathy patients with cancer were significantly lower than those in idiopathic membranous nephropathy patients without cancer ( P<0.01). Conclusion: The absence of glomerular PLA2R deposition and negative circulating anti-PLA2R antibodies, along with negative glomerular IgG4 staining, may be useful clues to more accurately screen underlying malignancies in membranous nephropathy patients.


2015 ◽  
Vol 42 (3) ◽  
pp. 250-257 ◽  
Author(s):  
Yang Gyun Kim ◽  
Young-Wook Choi ◽  
Se-Yun Kim ◽  
Ju Young Moon ◽  
Chun-Gyoo Ihm ◽  
...  

Background: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. Methods: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. Results: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). Conclusion: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.


Author(s):  
Brunetta Porcelli ◽  
Andrea Guarnieri ◽  
Fabio Ferretti ◽  
Guido Garosi ◽  
Lucia Terzuoli ◽  
...  

Abstract Background Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. Methods The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. Results According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. Conclusion Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.


2016 ◽  
Vol 43 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Shi-Yao Wei ◽  
Yu-Xiao Wang ◽  
Jian-Si Li ◽  
Shi-Lei Zhao ◽  
Tian-Tian Diao ◽  
...  

Background: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA2R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA2R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA2R and sPLA2R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA2R or sPLA2R-Ab positive. The sPLA2R-Ab titre, not gPLA2R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA2R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA2R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA2R intensity and outcome. Conclusions: These data indicate that sPLA2R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA2R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Haoyuan Cui ◽  
Chao Li ◽  
Hang Li ◽  
Yu-bing Wen ◽  
Xi-wei Yan ◽  
...  

Abstract Background and Aims IgG subclass switch phenomenon in early pathological stage of idiopathic membranous nephropathy (IMN) was reported recently. However, the profile of serum anti-phospholipase A2 receptor (PLA2R) antibody and glomerular PLA2R antigen was not reported in previous studies. The objective of our study was to testify whether glomerular IgG subclass switch phenomenon was present in PLA2R-related and PLA2R-unrelated IMN, respectively. Method This was a retrospective study including 157 Chinese patients with biopsy-proven IMN in a tertiary referral hospital between September 2017 and November 2019. IMN patients were classified into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroups. We compared the immunofluorescence intensity of glomerular IgG subclass between two groups among different electron microscopic (EM) stages. Results Positive rate of anti-PLA2R antibody was 56.0% (88/157) and glomerular PLA2R deposition was 75.8% (119/157). The intensity of IgG4 deposition in PLA2R-related group was stronger than that in unrelated group (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001). In stage I, IgG4 showed difference in predominant or co-dominant rate (pre/co rate) between two groups (P = 0.015). IgG4 was predominant in early stage (stage I) of both groups (pre/co rate 97% vs 57%). IgG1 was the less predominant subtype in stage I (pre/co rate 39% vs 43%). Pre/co rate of IgG3 declined with EM stage (P = 0.013). Conclusion IgG subclass switch were not found in PLA2R-related or unrelated IMN. IgG4 was the predominant IgG subtype in all stages of PLA2R-related IMN. The positive rate of glomerular PLA2R antigen was higher than serum PLA2R antibody.


2021 ◽  
Author(s):  
ting li ◽  
qingqing wu ◽  
Xue Yang ◽  
Yueming liu ◽  
bo lin ◽  
...  

Background: The level of serum antibodies against the M-type phospholipase A2 receptor (anti-PLA2R-IgG) is closely related to the disease activity of idiopathic membranous nephropathy (IMN). Therefore, the establishment of a...


2013 ◽  
Vol 24 (4) ◽  
pp. 677-683 ◽  
Author(s):  
Marieke J.H. Coenen ◽  
Julia M. Hofstra ◽  
Hanna Debiec ◽  
Horia C. Stanescu ◽  
Alan J. Medlar ◽  
...  

2021 ◽  
Author(s):  
Dan Gao ◽  
Li-Ping Lu ◽  
Zhi-Guo Zhao

Abstract Background Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN. Methods A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity. Results The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including phospholipase A2 receptor (PLA2R), thrombospondin type I domain-containing 7A (THSD7A), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLA2R for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%. Conclusions This meta-analysis shows that PLA2R and THSD7A are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN. At the same time, other new diagnostic biomarkers in IMN need to be found in the future.


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