Antibody levels of M type phospholipase A2 receptor in patients with membranous nephropaty and nephrotic syndrome

  • Antonio Vilches Sección Nefrología, Servicio de Medicina Interna, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
  • María Elena Biaiñ Sección Nefrología, Servicio de Medicina Interna, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
  • Gustavo Laham Sección Nefrología, Servicio de Medicina Interna, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
  • Carlos Díaz Sección Nefrología, Servicio de Medicina Interna, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
  • Carolina Carrizo Sección Reumatología, Servicio de Laboratorio, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
  • Roberto Iottti Servicio de Anatomía Patológica, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
Keywords: membranous nephropathy, anti phospholipase A 2 antibody, nephrotic syndrome, Anti-PLA2R dosage

Abstract

Introduction: Primary membranous nephropathy is one of the most frequent histological and immunohistochemical phenotypes in adult patients with nephrotic syndrome. With the identification of the M-type phospholipase A2 receptor (PLA2R), detection of serum anti-PLA2 has changed the diagnostic approach, the control of therapeutic efficacy and the evolution follow-up of this nephropathy. In most series, about 70% of MN treatment-naive patients test positive for this antibody. Objective: Our aim is to ascertain antibody level in MN patients and in nephrotic syndrome patients. Methods: In this retrospective observational study, 101 patients were evaluated (86 cases of MN diagnosed by renal biopsy and 15 with no pathologic diagnosis). They underwent the anti-PLA2R test. Demographic data, lab results (creatinine, albumin, proteinuria), renal histopathology and treatments administered were analyzed. We split MN patients diagnosed by renal biopsy into two groups according to anti-PLA2R results: Positive (those having values ≥ 20 U/mL) and Negative ([n=56] values ≤ 14 U/mL). Patients with equivocal results were not included. Results: From the total number of PMN patients diagnosed by renal biopsy, 29% (n=25) were positive for anti-PLA2R; 5.8% (n=5) had equivocal results, and 65.2% (n=56) were negative. Only 1 of the 15 patients suffering from nephrotic syndrome with no pathologic diagnosis was positive for anti-PLA2R. Anti-PLA2R testing results were positive for 47.7% of patients in a subgroup (n=35) that underwent the test no more than months after renal biopsy. No significant differences were found between the anti-PLA2R positive (n=25) and negative (n=56) groups regarding age, sex, albumin level, plasmatic creatinine and proteinuria. Conclusions: In our sample we obtained a low percentage of anti-PLA2R positivity compared to what was reported in the literature. Anti-PLA2R testing should be performed at the beginning of a nephrotic syndrome, prior to any treatment so as to determine the need of a renal biopsy, or with the result of a renal biopsy to determine if it is a primary or secondary form and evaluate the response to drugs or to “active surveillance

References

1) Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient's care. Lancet. 2015;385(9981):1983-92. doi: 10.1016/S0140-6736(15)60731-0.

2) Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11-21. doi: 10.1056/NEJMoa0810457.

3) Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014;371(24):2277-87. doi: 10.1056/NEJMoa1409354.

4) Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross LA, et al. Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int. 2020;97(1):163-74. doi: 10.1016/j.kint.2019.09.014.

5) Hihara K, Iyoda M, Tachibana S, Iseri K, Saito T, Yamamoto Y, et al. Anti-Phospholipase A2 receptor (PLA2R) antibody and glomerular PLA2R expression in japanese patients with membranous nephropathy. PLoS One. 2016;11(6):e0158154. doi: 10.1371/journal.pone.0158154.

6) Beck LH Jr, Salant DJ. Membranous nephropathy: from models to man. J Clin Invest. 2014;124(6):2307-14. doi: 10.1172/JCI72270.

7) Cravedi P, Abbate M, Gagliardini E, Galbusera M, Buelli S, Sabadini E, et al. Membranous nephropathy associated with IgG4-related disease. Am J Kidney Dis. 2011;58(2):272-5. doi: 10.1053/j.ajkd.2011.05.002.

8) Francis JM, Beck LH Jr, Salant DJ. Membranous nephropathy: a journey from bench to bedside. Am J Kidney Dis. 2016;68(1):138-47. doi: 10.1053/j.ajkd.2016.01.030.

9) Xie Q, Li Y, Xue J, Xiong Z, Wang L, Sun Z, et al. Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy. Am J Nephrol. 2015;41(4-5):345-53. doi: 10.1159/000431331.

10) Stehlé T, Audard V, Ronco P, Debiec H. Phospholipase A2 receptor and sarcoidosis-associated membranous nephropathy. Nephrol Dial Transplant. 2015;30(6):1047-50. doi: 10.1093/ndt/gfv080.

11) Bobart SA, De Vriese AS, Pawar AS, Zand L, Sethi S, Giesen C, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int. 2019;95(2):429-38. doi: 10.1016/j.kint.2018.10.021.

12) Hofstra JM, Debiec H, Short CD, Pellé T, Kleta R, Mathieson PW, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23(10):1735-43. doi: 10.1681/ASN.2012030242.

13) Jiang Z, Cai M, Dong B, Yan Y, Yang Y, Wang M, et al. Clinicopathological features of atypical membranous nephropathy with unknown etiology in adult chinese patients. Medicine (Baltimore). 2018;97(32):e11608. doi: 10.1097/MD.0000000000011608.

14) Díaz M, Agraz I, Soler MJ. Anti-phospholipase A2 receptor antibody and spontaneous remission in membranous nephropathy. Clin Kidney J. 2019;12(1):33-5. doi: 10.1093/ckj/sfy079.

15) Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA, Aslam N, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 2019;381(1):36-46. doi: 10.1056/NEJMoa181442.

16) Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, et al. Rituximab for severe membranous nephropathy: a 6-month trial with extended follow-up. J Am Soc Nephrol. 2017;28(1):348-58. doi: 10.1681/ASN.2016040449.

17) Wu X, Liu L, Guo Y, Yang L. Clinical value of a serum anti-PLA2R antibody in the diagnosis and monitoring of primary membranous nephropathy in adults. Int J Nephrol Renovasc Dis. 2018;11:241-7. doi: 10.2147/IJNRD.S176665.

18) Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pellé T, Gaspari F, et al. Anti-Phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol. 2015;26(10):2545-58. doi: 10.1681/ASN.2014070640.

19) Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011;22(8):1543-50. doi: 10.1681/ASN.2010111125.

20) Bomback AS. Management of membranous nephropathy in the PLA2R era. Clin J Am Soc Nephrol. 2018;13(5):784-86. doi: 10.2215/CJN.12461117.

21) García-Vives E, Solé C, Moliné T, Alvarez-Ríos AM, Vidal M, Agraz I, et al. Antibodies to M-type phospholipase A2 receptor (PLA2R) in membranous lupus nephritis. Lupus. 2019;28(3):396-405. doi: 10.1177/0961203319828521.
Published
2020-12-15
How to Cite
1.
Vilches A, Biaiñ ME, Laham G, Díaz C, Carrizo C, Iotti R. Antibody levels of M type phospholipase A2 receptor in patients with membranous nephropaty and nephrotic syndrome. Rev Nefrol Dial Traspl. [Internet]. 2020Dec.15 [cited 2024Nov.22];40(4):283-94. Available from: http://revistarenal.org.ar/index.php/rndt/article/view/569
Section
Original Article