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| Year : 2023 | Volume
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| Issue : 2 | Page : 269-277 |
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| Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India |
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Sriranjan Mukherjee1, Abhishek Kumar2, Priyanka Maity1, Moumita Sengupta1, Keya Basu1, Arpita Ray Chaudhury2, Manimoy Bandopadhyay3, Bidhan Chandra Chakraborty4
1 Department of Pathology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Nephrology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
3 Director, Department of Anatomy, Reasearch Scientist – I, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
4 Department of Medical Research Unit, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
Click here for correspondence address and email
| Date of Submission | 24-Feb-2021 |
| Date of Decision | 07-Apr-2021 |
| Date of Acceptance | 15-Apr-2021 |
| Date of Web Publication | 06-Jun-2022 |
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 Abstract | | |
Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.
Keywords: ELISA, membranous nephropathy, paraffin immunoflourescence, Phospholipase A2 Receptor (PLA2R)
How to cite this article:
Mukherjee S, Kumar A, Maity P, Sengupta M, Basu K, Chaudhury AR, Bandopadhyay M, Chakraborty BC. Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India. Indian J Pathol Microbiol 2023;66:269-77 |
How to cite this URL:
Mukherjee S, Kumar A, Maity P, Sengupta M, Basu K, Chaudhury AR, Bandopadhyay M, Chakraborty BC. Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Jun 3];66:269-77. Available from: https://www.ijpmonline.org/text.asp?2023/66/2/269/346690 |
| Introduction | |  |
Membranous nephropathy (MN) is a pattern of glomerular injury either idiopathic in nature or associated with wide range of diseases sharing a common pathogenesis. The evaluation begins with recognition of the clinical finding of nephrotic syndrome especially in adults which leads to a renal biopsy. The term membranous pattern of injury refers to the uniform diffuse and global thickening with subepithelial argyrophillic spikes along glomerular basement membrane (GBM) on light microscopy.[1] Unfortunately, routine immunofluorescence findings fail to unveil the etiological association unlike immunopathological classification scheme used in membranoproliferative or crescentic glomerulonephritis.[2],[3] But exact etiological categorization is essential as individualized treatment needs to be administered and outcomes are also variable.
In around 85% of cases, MN occurs in absence of any known etiology or systemic disease where it is known as primary membranous nephropathy (PMN). In the remaining cases, MN occur secondary to other disorders, like malignant tumors, infections, SLE, drugs etc., and is known as secondary membranous nephropathy (SMN). Discovery of an endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) was a breakthrough in the pathogenesis of PMN.[4] PLA2R combines with the anti-PLA2R antibodies produced in the body, to form the in situ immune complex that activates the complement system to cause podocyte injury. PLA2R is a type I transmembrane glycoprotein member of the mannose receptor family expressed on the glomerular podocytes. It has a conserved extracellular structure consisting of the cysteine rich (Ricin B) domain (Cys-R), a fibronectin II domain, and a tandem repeat of 8 C type lectin domains (CTLD 1–8).[5],[6] Anti-PLA2R-reactive epitopes are conformation dependent and have been identified in three domains: Cys-R, CTLD1, and CTLD7.[7],[8]
It has been shown that serum anti-PLA2R antibody is also useful biomarker in predicting the prognosis and guiding treatment apart from establishing the diagnosis of PMN.[9],[10],[11],[12],[13],[14] There have been studies that have analyzed renal tissue PLA2R expression in MN and the worldwide incidence are quite variable.[15],[16],[17] But there are only a handful of studies regarding the same from our population.[18]
In this study, we examined renal biopsy specimen and looked for histological features of MN including immunofluorescence findings. We analyzed renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases. We aimed to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of tissue PLA2R and serum anti-PLA2R antibodies for detecting PMN.
[TAG:2]Materials and Methods[/TAG:2]
This was a prospective study carried out in the department of Pathology in collaboration with department of Nephrology of our institute from March 2019 to August 2020. The study was carried out in accordance with the ethical principles stated by the Declaration of Helsinki Principles and was approved by the Institutional ethical committee.
The study comprised of 61 cases of MN that were diagnosed on USG-guided percutaneous biopsy specimens of kidney. Patient's age ranging from 18 years to 80 years old were included in the study.
Kidney biopsy (light microscopy and immunoflourescence) was analyzed by two trained nephropathologist in the division of nephropathology at department of pathology. Two cores of renal tissue were obtained—one core was kept in 10% neutral buffered formalin for histopathological examination and the stains used were haematoxylin and eosin stain (H&E), periodic acid Schiff (PAS), MassonTrichrome (MT), and Jone's methanamine silver (JMS). Initially the membranous pattern of injury was identified by looking for diffuse and global glomerular basement membrane (GBM) thickening with appreciable spikes or holes in JMS stain.[15] The histological parameters we assessed were: total number of glomeruli, percentage of glomeruli with focal or global glomerulosclerosis, evidence of mesangial matrix expansion or hypercellularity, nature of GBM changes in JMS stain, degree of tubulointerstitial chronicity (Interstitial Fibrosis and Tubular Atrophy-IFTA) and presence of arteriolar pathology.
For immunofluorescence evaluation we received sample in cold normal saline. The frozen sections were stained with FITC conjugated polyclonal rabbit anti-sera against human IgG, IgM, IgA, C3, C1q, kappa and lambda (DAKO, Germany). Immunofluorescence findings were categorized from (+) to (++++) scale according to intensity. Location and pattern of staining were also documented. Control slides were also examined simultaneously. Immunofluorescence, characteristic of MN was fine granular GBM positivity of more than 2 + intensity.[19]
Determination of sample size was done using www.openepi.com – Version 3.[20]
We calculated the sample size using following formula:
Sample size n = [DEFF*Np (1-p)]/[(d2/Z21-α/2*(N-1)+p*(1-p)]
Considering 90% confidence interval 80 patients were initially included in the study. But 19 patients were subsequently eliminated because of history of glucocorticoids and immunosuppressive intake and non-availability of the patient for collection of serum sample or insufficient formalin fixed paraffin embedded tissue for PLA2R immunofluorescence. We have also excluded the patient's with transplanted kidney.
Details of history and clinical examinations were documented from the data provided in the requisition form. The investigations that were carried out were urine routine biochemical examination, urine microscopic examination, urine culture and sensitivity, 24 h urine protein, complete blood counts, coagulation profile, serum albumin, BUN and creatinine levels, lipid profile, serum sodium and potassium levels, fasting and post prandial blood sugar level. Serological tests were done for anti-dsDNA antibody, antinuclear antibody (ANA), C3&C4, cANCA and pANCA, HbsAg and Anti-HCV, syphilis and HIV. Some of these tests were part of routine investigation while others were done to rule out secondary causes of MN. An ultrasonography of kidney, ureter, and bladder was performed. Investigations performed to rule out the possibility of malignancy were chest X-ray, abdominal ultrasonogram, microscopic urine examination for atypical cells, stool examination for occult blood, mammograms andserum prostate specific antigen levels. History of drug intake was taken to rule out drug induced MN.
Criteria for PMN were: (1) biopsy-proven cases of membranous pattern of injury; (2) normal complement level; (3) negative results for ANA, anti-dsDNA, ANCA, cryoglobulins, and viral markers (HbsAg and HIV); (4) no appreciable signs of cancer. Those patients with any identifiable secondary cause were categorized as SMN.[21]
Anti-PLA2R antibody estimation was performed on the baseline sera in the Medical Research unit (MRU) of our institute. Quantitative serum antibody estimation was done by ELISA using commercially available kit (CKbio-12874). The manufacturer protocol was followed. The recommended cutoff values for anti-PLA2R antibody were: >20 RU/ml for positive titre, 14–20 RU/ml for borderline titre, and <14 RU/ml for negative titre.[14] Tissue staining for PLA2R antigen was done on formalin fixed paraffin embedded tissue using FITC linked rabbit polyclonal anti-PLA2R antibodies (Sigma--Aldrich, dilution of 1:50). Each batch was run with positive and negative control. The stain was evaluated by standard immunofluorescence microscopy. Granular staining of PLA2R along the capillary wall was considered positive.[22] In case of equivocal staining or discrepancy with serum anti-PLA2R antibody results, the tissue staining for PLA2R was repeated.
According to KDIGO guideline, combination of cyclical corticosteroid and a cytotoxic agent-modified ponticelli regimen was administered as the initial treatment of choice. Certain investigations were monitored 24 h urine protein, serum creatinine, albumin, and total cholesterol. Depending on the response, the patients were categorized into three groups: complete remission, partial remission, and non-remission after treatment.[23]
Normally distributed continuous variables were expressed as mean and range. Comparison between groups was done using paired Student's t-test. Categorical variables were expressed as percentages, and compared between the groups using Fischer's exact test or Chi-square test. All statistical analyses were done using SPSS 19.0 software. P value of < 0.05 was considered to be statistically significant.
| Results | | |
Clinical and biochemical finding
Sixty-one patients were included in the study out of which 33 (54.1%) were males and 28 (45.9%) were females. The mean age of the patients was 36.52 ± 13.97 years. Out of 61 cases, 29 (47.5%) had PMN and 32 (52.5%) had SMN. The causes of secondary MN in our study were systemic lupus nephritis (n = 19), hepatitis C (n = 2), malignancy (n = 2), hepatitis B (n = 1), Sjogren's syndrome (n = 1), rheumatoid arthritis (n = 1), ANCA associated (n = 1), Hashimoto thyroiditis (n = 1), HIV (n = 1), malaria (n = 1), tuberculosis (n = 1), and NSAID intake (n = 1). Out of 61 patients, one suffered from diabetes mellitus, 3 were obese, and 19 were hypertensive. Mean age of PMN (41.58 ± 13.50 years) was higher than SMN (31.93 ± 12.95 years). Out of 29 PMN cases, 22 were male and 7 were female, whereas out of 32 SMN cases, 11 were male and 21 were female. Sixteen out of 19 cases of SLE were female. There was significant difference in mean age and gender distribution between PMN cases and SMN cases. Mean 24 h urine protein levels of PMN and SMN were 4.24 ± 1.96 gm and 3.69 ± 1.61 gm, respectively, mean serum C3 levels of the same were 114.57 ± 13.6 mg/dl and 78.32 ± 32.50 mg/dl, respectively, and mean serum creatinine levels were 1.45 ± 1.10 mg/dl and 1.46 ± 1.86 mg/dl, respectively. 19 out of 61 patients showed serum ANA positivity. The difference in mean serum C3 level between PMN cases and SMN cases was significant while the differences were not significant in case of mean urinary protein level and mean serum creatinine level. The mean serum creatinine level (in mg/dl) for SLE, Sjogren syndrome, ANCA associated disorder, Hashimoto thyroiditis, Hepatitis B, HIV, Rheumatoid arthritis, Malaria, Tuberculosis, malignancy, hepatitis C and patients with NSAID intake were 0.97, 0.6, 3.9, 0.91, 1.2, 0.8, 0.8, 3.4, 0.8, 0.9, 6.2, and 0.7, respectively. The mean 24 h proteinuria level (in gm) for the same were 3.85, 1.5, 5.2, 4.7, 2.3, 1.3, 1.9, 4.2, 7.6, 3.98, 4.5, and 1.8, respectively. [Table 1] and [Table 2] | Table 1: Comparative analysis of clinical and laboratory details of Primary and Secondary MN
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Pathologic features
On histopathological examination, average number of glomeruli detected in PMN and SMN was 13 and 12, respectively. In our study, <10% global glomerulosclerosis was found in 20 PMN cases and 25 SMN cases. Three cases of PMN and 4 cases of SMN revealed 10–25% global glomerulosclerosis. 6 cases of PMN and 2 cases of SMN were associated with 25–50% global glomerulosclerosis. Only a single case of SMN showed >50% global glomerulosclerosis. Segmental glomerulosclerosis was found in 14 cases of PMN and 14 cases of SMN. Mesangial hypercellularity was present in 13 cases of PMN and 25 cases of SMN. The difference in expression of mesangial hypercellularity between PMN cases and SMN cases was significant (P = 0.007). In JMS stain, segmental irregularity in GBM was seen in 6 cases of PMN and none of SMN, the difference being significant (P = 0.006). Diffuse and global GBM thickening was seen in 23 cases of PMN and all 32 cases of SMN, the difference being significant (P = 0.006). Membrane spikes were noted in 20 cases of PMN and 24 cases of SMN [Figure 1]. Holes in GBM were present in 3 cases of PMN and 7 cases of SMN. We classified interstitial inflammation into 5 categories: Nil, Minimal (<10%), Mild (11%-25%), Moderate (26%-50%), and severe (>50%) that had 17, 1, 6, 3, 2, cases respectively of PMN and 17, 3, 7, 2, and 3 cases, respectively, of SMN. Interstitial fibrosis and tubular atrophy (IFTA) was classified into 5 categories: Nil, Minimal (<10%), Mild (11–25%), Moderate (26–50%), and severe (>50%) that had 8, 15, 0, 6, and 0 cases, respectively, of PMN and 6, 18, 2, 5, and 1 cases, respectively, of SMN. Seven cases of PMN and 6 cases of SMN showed features of arteriosclerosis [Table 3]. | Figure 1: Kidney biopsy finding- (a) Glomerulus with uniform diffuse and global basement membrane thickening along with segmental sclerosis with adhesion. (H&E stain; 200x); (b) Mesangial hypercellularity. (Periodic acid-Schiff stain; 200x); (c) Glomerulomegaly with uniform diffuse and global basement membrane thickening. (Masson Trichrome stain; 200x); (d) Diffuse argyrophillic spikes along basement membrane spikes (Silver methanamine stain; original magnification 200x)
Click here to view |
On immunofluorescence examination, all cases of PMN showed strong positivity of IgG along GBM. Positivity along GBM for IgA, IgM, C3 and C1q were found in 5, 8, 11, and 6 cases of PMN, respectively [Figure 2] and [Figure 3]. Four PMN cases revealed immune deposit along mesangium while 2 PMN cases showed light chain restriction. Out of 19 SLE cases, positivity along GBM for IgG, IgA, IgM, C3, and C1q were seen in 19, 13, 8, 10, and 13 cases, respectively. Six cases showed mesangial positivity and 2 cases showed light chain restriction. [Table 4] | Figure 2: Immunoflourescence microscopy shows (a) strong (3+), fine granular glomerular capillary wall staining by IgG.(200x, FITC); (b) negative IgA staining.(200x, FITC); (c) negative IgM staining.(200x, FITC); (d) negative C3c staining.(200x, FITC); (e) negative C1q staining.(200x, FITC); (f) strong (2+), fine granular glomerular capillary wall staining by kappa.(200x, FITC) (g) strong (2+), fine granular glomerular capillary wall staining by lambda.(200x, FITC)
Click here to view |
 | Figure 3: Immunoflourescence microscopy shows (a) strong (3+) fine granular capillary wall staining by IgG.(200x, FITC); (b) fine granular capillary wall staining by IgA (1+).(200x, FITC); (c) mesangial IgM (1+) with trace capillary wall positivity.(200x, FITC); (d) strong (3+), fine granular capillary wall staining by C3c (200x, FITC); (e) mesangial C1q (1+) with trace capillary wall positivity.(200x, FITC); (f) strong (2+), fine granular capillary wall staining by kappa.(200x, FITC) (g) strong (2+) fine granular capillary wall staining by lambda.(200x, FITC)
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 | Table 4: Comparison between Serum PLA2R level and Immunofluorescence characteristics of membranous GN
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PLA2R and its disease association
Out of 29 cases of PMN, 21 were positive (>14 RU/ml), 7 were negative (<14 RU/ml), and one had borderline value (14–20 RU/ml) for serum anti-PLA2R antibody. Out of 32 cases of SMN cases, only 2 cases showed serum anti-PLA2R antibody positivity, one being associated with malignancy and another with Hepatitis C infection (P < 0.001). Overall, sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively.
GBM positivity for PLA2R on paraffin immunofluorescence microscopy was seen in 22 out of 29 cases of PMN and in 2 out of 32 cases of SMN (P < 0.0001). Overall, sensitivity, specificity, PPV, and negative predictive value of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively [Figure 4]. | Figure 4: Immunoflourescence staining for PLA2R- (a) granular capillary wall (+++) staining (200x, FITC); (b) granular capillary wall (++) staining (200x, FITC); (c) Segmental granular capillary wall (+) staining (200x, FITC); (d) No capillary wall staining (0) (200x, FITC)
Click here to view |
Strong concordance between tissue PLA2R on paraffin immunofluorescence microscopy and serum anti-PLA2R antibody on ELISA was observed with kappa coefficient of 0.9023. All 21 PMN cases, positive for serum PLA2R, were ultimately positive for tissue PLA2R. There was a single case of PMN which showed positivity for tissue PLA2R but serum PLA2R had a borderline value. Among SMN cases, 2 cases were positive for both serum PLA2R and tissue PLA2R while two cases showed borderline value for serum PLA2R and negativity for tissue PLA2R. An ROC curve analysis identified cutoff for serum anti-PLA2R antibody for positivity to be 17.35RU/ml [Table 5].
Outcome and follow up
We could obtain follow-up data of 9 MN cases among which 4 achieved complete remission. The mean value of serum anti-PLA2R antibody among completely remitted patients was 35.9 RU/ml before treatment and 3.8 RU/ml after treatment, whereas in non-remitted patients it was 65.4 RU/ml and 12.0 RU/ml before and after treatment, respectively.
| Discussion | | |
Membranous nephropathy is a pattern of kidney injury with variable spectrum of etiological association and ultimately merges into end-stage renal disease in absence of timely intervention. Both exogenous factors (air pollution, smoking, and infection) and endogenous factors (human leukocyte antigen, increased antigen expression, and loss of tolerance) contribute in rise in worldwide incidence of this entity estimating 12 new cases per million of adults each year.[1],[9] But the pathophysiology of MN is an enigma for decades. Although the identification of autoantibodies either against PLA2R or thrombospondin type-1 domain-containing 7A (THSD7A) resolves the mystery in 75–80% of PMN, but in rest of the case it still remains unknown.[21] Ongoing research identifies novel proteins like Exostosin 1, Exostosin 2, and NELL-1 in these double negative cases.[24],[25]
Segregation into PMN and SMN is essential for administration of categorical management. The treatment of PMN consists of immunosuppressive agents, which are frequently associated with significant treatment complications, while in SMN the underlying disease has to be treated. A thorough clinical evaluation is essential to seek the secondary causes. Particular renal biopsy findings like mesangial hypercellularity, glomerular inflammatory cells, homogenous thickening of glomerular basement membrane in light microscopy, and full house positivity along with mesangial and extraglomerular immune depositions are suggestive of SMN over the PMN. But routine light and immunofluorescence examination fail to give exact categorical opinion as these prototypical features are not always confirmatory because of heterogeneity among individual disease and some overlapping exists.[1],[22] Similar findings were documented in our study also. It highlights the need for incorporation of additional serum or tissue specific biomarker in investigation protocol in case of membranous pattern of injury.
PLA2R is a major autoantigen in adult membranous nephropathy that is located in glomerular podocytes. Anti-PLA2R antibodies are formed leading to a large number of immune complex depositions which activates the either classical or alternative complement pathway depending on IgG subclass that in turn produces a membrane attack complex and damages the podocyte and GBM.[21] Studies have shown that the levels of serum anti-PLA2R antibodies in PMN patients are higher than those in normal and non-MN patients.[23] Tissue PLA2R analysis have also been done on renal biopsies and its variable expression in PMN have been demonstrated by various authors which may be attributed to ethnicity, disease heterogeneity and epitopes spreading on disease progression [Table 6].[15],[16],[17],[26]
Circulating anti-PLA2R antibody can be detected by three methods: Western blot, Indirect Immunofluorescence, and ELISA.[13] Out of these, we applied ELISA for antibody detection. Subramanian et al.[18] showed that the sensitivity and specificity of serum anti-PLA2R ELISA for PMN were 61.1% and 88.9%, respectively whereas we reported a higher sensitivity (91.3%) and a lower specificity (80%). They showed the sensitivity and specificity of tissue PLA2R staining for PMN to be 52.4% and 88.5%, whereas we reported the sensitivity and specificity of the same to be 91.67% and 81.08%, respectively. According to one international study, the autoantibody against PLA2R (anti-PLA2R) may be used to diagnose idiopathic MN (IMN). The cutoff value of 2.6RU/ml is recommended for the use of anti-PLA2R for the diagnosis of IMN.[27] We demonstrated a strong concordance between tissue PLA2R on immunoflourescence microscopy and serum PLA2R on ELISA with kappa coefficient of 0.9023 while the same in their study was 0.61 (moderate concordance). Although the manufacturer recommended cutoff values for anti-PLA2R antibody were: >20 RU/ml for positive titre a ROC curve analysis identified cutoff for serum anti PLA2R antibody for positivity to be 17.35 RU/ml.
The studies on Indian population have shown a prevalence of PLA2R related PMN to be 55–88% and that of PLA2R related SMN to be 0–3.7%. The testing methods applied were tissue PLA2R direct immunofluorescence or serum anti PLA2R ELISA or both. In our study we found that the prevalence of serum anti-PLA2R antibody among PMN cases and SMN cases were 72.4% and 6.3%, respectively. Subramanian et al.,[18] on combining the two testing methods demonstrated a prevalence of 72.8% of PLA2R related PMN and 16.7% of PLA2R related SMN. Both Gopalakrishnan et al.[13] and Subramanian et al.[18] found that PLA2R-positive MN cases had significantly more proteinuria than PLA2R-negative cases with good concordance between antibody titres and degree of proteinuria. But in our study, we did not find any correlation between PLA2R positivity and degree of proteinuria.
It was earlier thought that anti-PLA2R antibody was specific for PMN, but recently some studies have shown its positivity in SMN cases.[22],[23] While Gopalakrishnan et al.[13] reported that none of their 15 patients with SMN were positive for the antibodies, we reported two SMN cases that were positive for both serum PLA2R and tissue PLA2R. One had malignancy and the other had hepatitis C virus infection. Subramanian et al.[18] found 6 cases of SMN that were positive for tissue PLA2R out of which 5 had lupus MN and 1 had hepatitis B associated MN. It is not clear if PLA2R positivity in SMN is because of simultaneous presence of unrelated systemic diseases in PMN patients. It is possible that the unrelated systemic diseases like tuberculosis, hepatitis C and cancer could be driving the disease process despite PLA2R positivity. The inflammatory milieu present in these conditions might be triggering the onset of PMN.[28],[29] That PLA2R autoantibodies are produced because of an aberrant expression of PLA2R epitopes by the granuloma in sarcoidosis associated MN or by tumor cells in neoplasm-associated MN needs to be explored.
In the 9 patients that were followed up, we found that baseline serum anti-PLA2R antibody in patients who underwent complete remission was less than that in non-remitted patients. We also noted that the reduction in serum anti-PLA2R antibody was more in patients who had complete remission than that in non-remitted patients. Thus, serum PLA2R-ab acts as not only a diagnostic marker but also a pivotal predictor for clinical remission. Wu et al.[23] had similar observations. They reported that the serum levels of anti-PLA2R antibodies in the non-remission group were significantly higher than those in the complete remission group and partial remission group and antibody levels after treatment were significantly lower than that before treatment in the complete remission group and the partial remission group, while there was no significant difference in antibody levels after treatment compared with before treatment in the non-remission group. Zhang QH et al.[30] analyzed the correlation between several clinical biomarker like 24-h urine protein, serum albumin, creatinine, urea, and eGFR with PLA2R-Ab in Sera or PLA2R-Ag in Kidneys. They found good correlation with serum PLA2R-Ab than renal PLA2R-Ag. Therefore, sPLA2R-ab can be considered as a prognostic factor for stratifying PMN patients.
Limitation of our study: In our study, because of limited number of follow-up cases, the prognostic utility of serial serum PLA2R analysis could not be evaluated.
| Conclusion | | |
The treatment of MN depends on whether the disease is primary or secondary. The distinction between PMN and SMN is done by clinical evaluation but both light microscopy and routine immunofluorescence examination fail to unveil etiological association. We found serum anti PLA2R antibody detection and renal tissue PLA2R analysis to be sensitive and specific in detecting PMN. Baseline serum anti PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker for evaluation of PMN.
Acknowledgements
We are very grateful to Mrs Madhumita Mondal and Mr Ashin Ghosh for performing all the laboratory procedures in our nephropathology division.
Financial support and sponsorship
Medical Research Unit, IPGME&R.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Moumita Sengupta
244 AJC Bose Road, Kolkata - 700 020, West Bengal
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijpm.ijpm_210_21
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] |
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