Abstract
Background
Detection of M-type phospholipase A2 receptor (PLA2R) can be used in serologic diagnosis of idiopathic membranous nephropathy (IMN), but there are limited data about the sensitivity and specificity of its diagnostic values.
Methods and results
Meta-analysis of diagnostic test studies assessing the values of PLA2R in diagnosis of IMN. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of PLA2R to predict IMN. The quality of the studies was evaluated using the guidelines of the updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The results are summarized as sensitivity, specificity, and diagnostic odds ratio (OR). Data from 10 studies involving 1,550 participants were analyzed. Across all settings, the diagnostic OR for serum anti-PLA2R level to predict IMN at different stages was 247.41, with sensitivity of 0.69 and specificity of 0.99. The estimated sensitivity and specificity of serum anti-PLA2R level for diagnosis of IMN in the active stage were 74.0 and 95.0 %, respectively, with diagnostic OR of 54.22. The estimated sensitivity and specificity of biopsy anti-PLA2R for diagnosis of IMN at different stages was 73.0 and 83.0 %, respectively, with diagnostic OR of 13.75.
Conclusions
This meta-analysis shows that serum anti-PLA2R level is of diagnostic value for IMN in the active stage. Future large-cohort prospective studies are required to reveal the diagnostic value of circulating anti-PLA2R antibodies versus PLA2R antigens in kidney biopsy for IMN at different stages.
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References
Glassock RJ (2010) The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 56(1):157–167
Segal PE, Choi MJ (2012) Recent advances and prognosis in idiopathic membranous nephropathy. Adv Chronic kidney Dis. 19(2):114–119
Ronco P, Debiec H (2005) Molecular pathomechanisms of membranous nephropathy: from Heymann nephritis to alloimmunization. J Am Soc Nephrol 16(5):1205–1213
Waldman M, Austin HA 3rd (2009) Controversies in the treatment of idiopathic membranous nephropathy. Nat Rev Nephrol. 5(8):469–479
Ohara O, Ishizaki J, Arita H (1995) Structure and function of phospholipase A2 receptor. Prog Lipid Res 34(2):117–138
Ishizaki J, Hanasaki K, Higashino K et al (1994) Molecular cloning of pancreatic group I phospholipase A2 receptor. J Biol Chem 269(8):5897–5904
Hanasaki K, Arita H (2002) Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat 68–69:71–82
Beck LH Jr, Bonegio RG, Lambeau G et al (2009) M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361(1):11–21
Whiting P, Rutjes AWS, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536
Hoxha E, Harendza S, Zahner G et al (2011) An immunofluorescence test for phospholipase-A(2)-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 26(8):2526–2532
Qin W, Beck LH Jr, Zeng C et al (2011) Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 22(6):1137–1143
McGettigan B, Bundell C, Webb-Smith E, Hollingsworth P (2012) Anti-phospholipase A2 receptor antibodies-an evaluation of the clinical utility of a transfected cell based indirect immunofluorescence assay in the diagnosis of idiopathic membranous nephropathy. Intern Med J 42(Suppl 4):11
Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H (2012) Kidney biopsy is a sensitive tool for ret of PLA2R-related membranous nephropathy. Nephrol Dial Transplant 28(7):1839–1844
Behnert A, Fritzler MJ, Teng B et al (2013) An anti-phospholipase A2 receptor quantitative immunoassay and epitope analysis in membranous nephropathy reveals different antigenic domains of the receptor. PLoS ONE 8(4):e61669
Kanigicherla D, Gummadova J, McKenzie EA et al (2013) Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 83(5):940–948
Larsen CP, Messias NC, Silva FG, Messias E, Walker PD (2013) Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol 26(5):709–715
Oh YJ, Yang SH, Kim DK, Kang SW, Kim YS (2013) Autoantibodies against phospholipase A2 receptor in korean patients with membranous nephropathy. PLoS ONE 8(4):e62151
Hofstra JM, Debiec H, Short CD et al (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23(10):1735–1743
Granata F, Petraroli A, Boilard E et al (2005) Activation of cytokine production by secreted phospholipase A2 in human lung macrophages expressing the M-type receptor. J Immunol. 174(1):464–474
Silliman CC, Moore EE, Zallen G et al (2002) Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase release and adhesion. Am J Physiol Cell Physiol 283(4):C1102–C1113
Beck LH Jr, Fervenza FC, Beck DM et al (2011) Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol 22(8):1543–1550
Beck LH Jr, Salant DJ (2010) Membranous nephropathy: recent travels and new roads ahead. Kidney Int 77(9):765–770
Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ (2011) Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 6(6):1286–1291
Debiec H, Ronco P (2011) PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 364(7):689–690
Prunotto M, Carnevali ML, Candiano G et al (2010) Autoimmunity in membranous nephropathy targets aldose reductase and SOD2. J Am Soc Nephrol 21(3):507–519
Bruschi M, Carnevali ML, Murtas C et al (2011) Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens. J Proteomics. 74(10):2008–2017
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S.-L. Hu and D. Wang contributed equally to this work.
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Hu, SL., Wang, D., Gou, WJ. et al. Diagnostic value of phospholipase A2 receptor in idiopathic membranous nephropathy: a systematic review and meta-analysis. J Nephrol 27, 111–116 (2014). https://doi.org/10.1007/s40620-014-0042-7
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DOI: https://doi.org/10.1007/s40620-014-0042-7