P0382“FALSE” POSITIVITY OF SERUM ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY (ANTI-PLA2R AB) IN PATIENTS WITH NON MEMBRANOUS GLOMERULAR DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irene Mok ◽  
Jason Choo

Abstract Background and Aims Phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN) and the detection of circulating autoantibodies to PLA2R (Anti-PLA2R Ab) is a major advance in understanding this disease. In this study, we aimed to determine if Anti-PLA2R Ab serves as a specific marker for PMN in our multi-ethnic Southeast Asian cohort. Method This was a prospective cohort study of all adults with glomerular disease undergoing biopsy between 1st January 2015 and 30th June 2018. Anti-PLA2R antibody levels were quantitatively determined by IgG ELISA (Euroimmun). Results are expressed as RU/ml. We considered a value of >20RU/ml to represent a positive result, value of <14RU/ml to be negative and values between 14-20 RU/ml to be indeterminate. Results Out of the cohort of 192 patients, there were 27 patients with Membranous Nephropathy (MN), with 12 PMN and 15 with secondary MN (SMN). Secondary causes were Hepatitis (1), Malignancy (1), Lupus (13). In our analyses, 10 (83.3%) PMN pts were positive for Anti-PLA2R Ab, with 7(58.3%) strongly positive with titres >200RU/ml and 2(16.7%) negative. For SMN, the majority, 12 out of 14 patients (85.7%) tested negative and the remaining 2 (7.7%) yielded values of indeterminate levels. Of note, among the 165 patients with non membranous glomerular disease, there were 15 patients (9.1%) with indeterminate Anti-PLA2R Ab levels and 31 patients (18.9%) tested positive for Anti-PLA2R antibody, with levels >20 RU/ml. Of these 31 patients, the majority of the patients had low levels of Anti-PLA2R Ab of <50 RU/ml. However there were 5 patients who had considerably high levels of Anti-PLA2R Ab of >50 RU/ml and their characteristics are tabled below (Table 1) Conclusion Consistent with other published studies, positive Anti-PLA2R antibody levels were highly specific for PMN in our multi-ethnic Southeast Asian population and our centre has since been consistently using this test for differentiating between PMN and SMN. What is most striking in our study is that we have found high-titre Anti-PLA2R antibody positivity in non-MN patients, which has not been frequently reported in literature. The unifying feature amongst these patients appear to be the presence of arterial and arteriolar sclerosis which is usually non-specific. Though we would not normally do the Anti-PLA2R antibody test in a patient with low suspicion of MN, our study findings warrants further investigation and may indicate the limited usefulness of Anti-PLA2R antibody levels as a screening tool for glomerulonephritis.

2019 ◽  
Vol 12 (1) ◽  
pp. 27-32
Author(s):  
Yosuke Inaguma ◽  
Atsutoshi Shiratori ◽  
Taku Nakagawa ◽  
Kyoko Kanda ◽  
Makiko Yoshida ◽  
...  

Background: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.


2018 ◽  
Vol 48 (6) ◽  
pp. 438-446 ◽  
Author(s):  
Zhen Qu ◽  
Mu-fan Zhang ◽  
Zhao Cui ◽  
Jia Wang ◽  
Miao Wang ◽  
...  

Background: Anti-phospholipase A2 receptor (PLA2R) antibodies are specific to the diagnosis of primary membranous nephropathy (pMN). The prevalence of positive antibodies varies among different cohorts. Still there is discrepancy in regard to the association between antibody levels and clinical courses, and the prognostic value of antibodies to treatment responses and kidney outcomes. Methods: Three hundred fifty-nine consecutive kidney biopsy-proven pMN patients were enrolled. Anti-PLA2R antibodies were detected by immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). Results: The positive rate of anti-PLA2R antibodies in pMN was 65.2% (234/359) by IFA and 56.3% (202/359) by ELISA. The antibody level presented positive correlation with urinary protein excretion (r = 0.164, p = 0.002). Detectable antibodies and a higher level of proteinuria were independent risk factors to no-remission after treatments (OR 3.15, p = 0.004; OR 1.11, p = 0.006) and were independent risk factors to no-spontaneous remission (OR 2.20, p = 0.011; OR 1.36, p < 0.001). A higher level of antibodies (hazard ratio 1.002, p = 0.019) was the independent risk factor to kidney dysfunction during follow-up. The antibodies turned negative in 42 out of 52 (80.8%) patients who achieved clinical remission, while they remained positive in all patients of the no-response category (p < 0.001). Conclusion: We documented correlations between anti-PLA2R antibody levels and clinical severity in this large Chinese pMN cohort. Antibody positivity and higher antibody level might predict treatment responses and kidney outcomes of pMN.


2017 ◽  
Vol 10 (2) ◽  
pp. 209-214 ◽  
Author(s):  
Perrine Jullien ◽  
Barbara Seitz Polski ◽  
Nicolas Maillard ◽  
Damien Thibaudin ◽  
Blandine Laurent ◽  
...  

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