CIRCULATING PHOSPHOLIPASE A2 RECEPTOR ANTIBODIES IN PRIMARY MEMBRANOUS NEPHROPATHY

AIM OF THE STUDY: evaluation of clinical significance of circulating antibodies to transmembrane phospholipase A2 M-type receptor of podocytes (anti-PLA2R Ab) in patients with primary membranous nephropathy (MN) on the top of already administered therapy. PATIENTS AND METHODS. 20 proved or prospectively observed patients with primary membranous nephropathy on symptomatic treatment with or without immunosuppressive therapy were included into observational study. Clinical data obtained at the moment of biopsy and during prospective follow-up included: gender, age, serum creatinine and albumin concentration, daily proteinuria (DP), AP, estimated glomerular filtration rate. Median of prospective follow-up was 525 (265- 1030) days. Anti-PLA2R Ab of IgG class was detected after treatment by indirect immunofluorescence. RESULTS. Anti-PLA2R Ab was found in 7 patients (group 1) and was absent in 13 (group 2) of 20 patients studied. There were no differences in level of proteinuria, albuminemia, AP and renal function at the time of biopsy. There were no significant changes in level of proteinemia, albuminemia and cases of clinical remissions in group 1 during treatment; in group 2 DP decreased significantly in contrast to initial value, serum albumin level practically normalized and clinical remission was achieved in all patients (3 cases – partial, 10 cases – complete). All cases of complete remission were observed after corticosteroids and cyclosporine combined therapy. CONCLUSION. Absence of anti-PLA2R Ab in patients on therapy is associated with achievement of clinical remission of primary MN; this test can be applied for monitoring of the disease activity, evaluation of treatment efficacy and prognosis.

1. Beck LH Jr, Bonegio RG, Lambeau G. et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361: 11–21

2. Stanescu HC, Arcos-Burgos M, Medlar A. et al. Risk HLADQA1 and PLA2R1 alleles in idiopathic membranous nephropathy. N Engl J Med 2011;364: 616–626

3. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 2011; 364: 689–690

4. Kerjaschki D, Farquhar MG. Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med 1983; 157: 667–686

5. Qin W, Beck LH Jr, Zeng C. et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011;22(6):1137-1143 6. Hofstra JM, Beck LH Jr, Beck DM. et al. Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011; 6: 1286–1291

6. Beck LH, Fervenza FC, Beck DM. et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol 2011;22: 1543–1550

7. Passerini P, Ponticelli C. Membranous nephropathy. In: Ponticelli C, Glassock R (eds). Treatment of Primary Glomerulonephritis, 2nd edn. Oxford University Press: Oxford, UK, 2009, pp 261–312

8. Levey AS, Stevens LA, Schmid CH et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150: 604–612

9. Смирнов АВ. Лечение гломерулопатий циклоспорином: правильный подход с неверным обоснованием. Нефрология 2010; 14(4):9-22

10. Jha V, Ganguli A, Saha TK et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephrol 2007; 18:1899–1904

11. Remuzzi G, Chiurchiu C, Abbate M. et al. Rituximab for idiopathic membranous nephropathy. Lancet 2002;360: 923–924

12. Ruggenenti P, Chiurchiu C, Brusegan V. et al. Rituximab in idiopathic membranous nephropathy: A one-year prospective study. J Am Soc Nephrol 2003;14: 1851–1857

13. Bomback AS, Derebail VK, McGregor JG. et al. Rituximab therapy for membranous nephropathy: A systematic review. Clin J Am Soc Nephrol 2009; 4: 734–744

14. Fervenza FC, Cosio FG, Erickson SB. et al. Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 2008; 73: 117–125

15. Cravedi P, Sghirlanzoni MC, Marasa M. et al. Efficacy and safety of rituximab second-line therapy for membranous nephropathy: A prospective, matched-cohort study. Am J Nephrol 2011; 33: 461–468

16. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012; 2(2): 139–274

17. Segarra A, Praga M, Ramos N. et al. Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients. Clin J Am Soc Nephrol 2009; 4: 1083–1088

18. Murtas C, Bruschi M, Candiano G. et al. Coexistence of Different Circulating Anti-Podocyte Antibodies in Membranous Nephropathy. Clin J Am Soc Nephrol 2012;7(9):1394-1400

19. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 2011; 364: 689–690