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Lupus-like membranous nephropathy during the postpartum period expressing glomerular antigens exostosin 1/exostosin 2 and phospholipase A2 receptor: a case report

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Abstract

Recently, several target antigens of membranous nephropathy (MN), such as phospholipase A2 receptor (PLA2R) and exostosin 1/exostosin 2 (EXT1/2), have been discovered. A 30-year-old woman was referred to our hospital with nephrotic range proteinuria and microscopic hematuria. She was first noted to have proteinuria before pregnancy, and her proteinuria worsened in the postpartum period. A renal biopsy showed MN. Immunofluorescence microscopy showed IgG, IgA, IgM, C3, C4, and C1q depositions in the mesangial area and glomerular capillary walls (GCWs). Regarding the IgG subclass, IgG1 and IgG3 were detected on glomeruli. Electron microscopy showed subepithelial electron-dense deposits (EDDs). EDDs were also detected in paramesangial and subendothelial areas. The diagnosis of membranous lupus nephritis (MLN) was suspected, but she did not fulfill the criteria for systemic lupus erythematosus. Neither anti-nuclear antibody nor hypocomplementemia were detected. We further evaluated glomerular EXT1/2 expressions, which were evident on GCWs. In addition, PLA2R was also detected on GCWs, although serum antibody for PLA2R was negative. She responded to immunosuppressive therapy with decreased proteinuria. In the present case, glomerular PLA2R expression implied the possibility of primary MN. However, pathological findings with a full-house staining pattern and glomerular EXT1/2 expressions were very similar to those of lupus-associated MN. Glomerular PLA2R expression appeared not to reflect immunocomplexes of PLA2R and autoantibody when considering the results for glomerular IgG subclass and the absence of serum anti-PLA2R antibody. Collectively, it is plausible that this was a case of a relatively young postpartum female who developed latent MLN rather than primary MN.

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References

  1. Cattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int. 2017;91(3):566–74.

    Article  PubMed  CAS  Google Scholar 

  2. Ronco P, Beck L, Debiec H, Fervenza FC, Hou FF, Jha V, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021;7(1):69.

    Article  PubMed  Google Scholar 

  3. Sethi S. New “antigens” in membranous nephropathy. J Am Soc Nephrol. 2021;32(2):268–78.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ronco P, Plaisier E, Debiec H. Advances in membranous nephropathy. J Clin Med. 2021;10(4):607.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, et al. Exostosin 1/exostosin 2-associated membranous nephropathy. J Am Soc Nephrol. 2019;30(6):1123–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Ravindran A, Casal Moura M, Fervenza FC, Nasr SH, Alexander MP, Fidler ME, et al. In patients with membranous lupus nephritis, exostosin-positivity and exostosin-negativity represent two different phenotypes. J Am Soc Nephrol. 2021;32(3):695–706.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wada Y, Iyoda M, Suzuki T, Tachibana S, Kanazawa N, Matsumoto K, et al. Immunopathological analysis of the expression of glomerular exostosin 1 and exostosin 2 in Japanese patients with lupus nephritis. Virchows Arch. 2021;479(5):997–1005.

    Article  PubMed  CAS  Google Scholar 

  10. Miyake K, Adachi K, Watanabe M, Sasatomi Y, Ogahara S, Abe Y, et al. Parasites alter the pathological phenotype of lupus nephritis. Autoimmunity. 2014;47(8):538–47.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ward F, Bargman JM. Membranous lupus nephritis: the same, but different. Am J Kidney Dis. 2016;68(6):954–66.

    Article  PubMed  Google Scholar 

  12. Iwakura T, Ema C, Isobe S, Fujikura T, Ohashi N, Kato A, et al. Prevalence of neural epidermal growth factor-like 1- and exostosin 1/exostosin 2-associated membranous nephropathy: a single-center retrospective study in Japan. Sci Rep. 2022;12(1):2967.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Wang C, Liu Y, Zhang M, Yang F, Xu F, Shi S, et al. Glomerular exostosin as a subtype and activity marker of class 5 lupus nephritis. Clin J Am Soc Nephrol. 2022;17(7):986–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. De Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC. A proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol. 2017;28(2):421–30.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Larsen CP, Messias NC, Silva FG, Messias E, Walker PD. Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol. 2013;26(5):709–15.

    Article  PubMed  CAS  Google Scholar 

  17. Gunnarsson I, Schlumberger W, Rönnelid J. Antibodies to M-type phospholipase A2 receptor (PLA2R) and membranous lupus nephritis. Am J Kidney Dis. 2012;59(4):585–6.

    Article  PubMed  Google Scholar 

  18. Garcia-Vives E, Solé C, Moliné T, Alvarez-Rios AM, Vidal M, Agraz I, et al. Antibodies to M-type phospholipase A2 receptor (PLA(2)R) in membranous lupus nephritis. Lupus. 2019;28(3):396–405.

    Article  PubMed  CAS  Google Scholar 

  19. Iwakura T, Ema C, Sato T, Isobe S, Fujikura T, Ohashi N, et al. Primary membranous nephropathy with enhanced staining of exostosin 1/exostosin 2 in the glomeruli: a report of 2 cases. Kidney Med. 2021;3(4):669–73.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Monga G, Mazzucco G, Basolo B, Quaranta S, Motta M, Segoloni G, et al. Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts. Mod Pathol. 1993;6(3):249–58.

    PubMed  CAS  Google Scholar 

  21. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

    Article  PubMed  CAS  Google Scholar 

  22. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yamazaki T, Takahashi H, Takeuchi K, Sakamoto E, Tominaga K, Sakurabayashi S, et al. Rare case of exostosin 1/exostosin 2-related membranous lupus nephritis concomitant with dual ANCA- and anti-GBM antibody-associated crescentic glomerulonephritis effectively diagnosed by mass spectrometry: a case report. BMC Nephrol. 2023;24(1):218.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Shearn MA, Hopper J Jr, Biava CG. Membranous lupus nephropathy initially seen as idiopathic membranous nephropathy Possible diagnostic value of tubular reticular structures. Arch Intern Med. 1980;140(11):1521–3.

    Article  PubMed  CAS  Google Scholar 

  25. Wen YK, Chen ML. Clinicopathological study of originally non-lupus “full-house” nephropathy. Ren Fail. 2010;32(9):1025–30.

    Article  PubMed  Google Scholar 

  26. Gianviti A, Barsotti P, Barbera V, Faraggiana T, Rizzoni G. Delayed onset of systemic lupus erythematosus in patients with “full-house” nephropathy. Pediatr Nephrol. 1999;13(8):683–7.

    Article  PubMed  CAS  Google Scholar 

  27. Yamada T, Itagaki F, Aratani S, Kawasaki S, Terada K, Mugishima K, et al. A case of membranous nephropathy diagnosed with lupus nephritis 11 years after onset. CEN Case Rep. 2019;8(4):301–7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sam R, Joshi A, James S, Jen KY, Amani F, Hart P, et al. Lupus-like membranous nephropathy: Is it lupus or not? Clin Exp Nephrol. 2015;19(3):395–402.

    Article  PubMed  CAS  Google Scholar 

  29. Simenhoff ML, Merrill JP. The spectrum of lupus nephritis. Nephron. 1964;1:348–75.

    Article  PubMed  CAS  Google Scholar 

  30. Adu D, Williams DG, Taube D, Vilches AR, Turner DR, Cameron JS, et al. Late onset systemic lupus erythematosus and lupus-like disease in patients with apparent idiopathic glomerulonephritis. Q J Med. 1983;52(208):471–87.

    PubMed  CAS  Google Scholar 

  31. Jennette JC, Iskandar SS, Dalldorf FG. Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. Kidney Int. 1983;24(3):377–85.

    Article  PubMed  CAS  Google Scholar 

  32. Yang AH, Lin BS, Kuo KL, Chang CC, Ng YY, Yang WC. The clinicopathological implications of endothelial tubuloreticular inclusions found in glomeruli having histopathology of idiopathic membranous nephropathy. Nephrol Dial Transplant. 2009;24(11):3419–25.

    Article  PubMed  Google Scholar 

  33. Shiiki H, Saito T, Nishitani Y, Mitarai T, Yorioka N, Yoshimura A, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int. 2004;65(4):1400–7.

    Article  PubMed  Google Scholar 

  34. Kallen RJ, Lee SK, Aronson AJ, Spargo BH. Idiopathic membranous glomerulopathy preceding the emergence of systemic lupus erythematosus in two children. J Pediatr. 1977;90(1):72–6.

    Article  PubMed  CAS  Google Scholar 

  35. Cairns SA, Acheson EJ, Corbett CL, Dosa S, Mallick NP, Lawler W, et al. The delayed appearance of an antinuclear factor and the diagnosis of systemic lupus erythematosus in glomerulonephritis. Postgrad Med J. 1979;55(648):723–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Orozco-Guillén AO, Abraham VS, Moguel Gonzalez B, Valdez Ortiz R, Ibarguengoitia F, Del Carmen ZM, et al. Kidney-limited full-house lupus-like membranous nephropathy and membranoproliferative glomerulonephritis in pregnancy. Kidney Int Rep. 2023;8(4):932–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Batra V, Kalra OP, Mathur P, Kavita, Dev G. Membranous glomerulopathy associated with placental site trophoblastic tumour: a case report. Nephrol Dial Transplant. 2007;22(6):1766–8.

    Article  PubMed  Google Scholar 

  38. Hoxha E, Thiele I, Zahner G, Panzer U, Harendza S, Stahl RA. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy. J Am Soc Nephrol. 2014;25(6):1357–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors greatly appreciate the excellent technical assistance provided by Ms. Naoko Ishigaki and Ms. Miki Hashimura.

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Authors and Affiliations

  1. Department of Nephrology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Ryoma Miyasaka, Yukihiro Wada, Kazuhiro Takeuchi, Tetsuya Abe, Ryota Uchitsubo, Sayumi Kawamura, Shun Sakurabayashi, Shokichi Naito, Togo Aoyama & Yasuo Takeuchi

  2. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan

    Kazuhiro Takeuchi & Akira Shimizu

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  1. Ryoma Miyasaka
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Correspondence to Yukihiro Wada.

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Miyasaka, R., Wada, Y., Takeuchi, K. et al. Lupus-like membranous nephropathy during the postpartum period expressing glomerular antigens exostosin 1/exostosin 2 and phospholipase A2 receptor: a case report. CEN Case Rep (2024). https://doi.org/10.1007/s13730-023-00848-w

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