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Ideal usage for differentiation of primary from secondary membranous nephropathy

Only patients with primary MN were found to be positive for anti-PLA2R autoantibodies in a retrospective analysis by Beck et al. All patients suffering from secondary MN were negative for these autoantibodies.1

 

Modified from: Beck et al., N Engl J Med 361, 11-21 (2009)
Modified from: Beck et al., N Engl J Med 361, 11-21 (2009)

However, in this study the serum samples had been taken nine months after performance of kidney biopsy, on average. Since five of the patients with secondary MN had also undergone immunosuppressive therapy, it is possible that anti-PLA2R which had potentially been present at the beginning of secondary MN had already disappeared by the time of sample withdrawal.1 To exclude an influence of the time point of sample withdrawal or therapy, a study was performed by Gunnarsson et al., who investigated whether autoantibodies against PLA2R exist at time of diagnosis of secondary MN. 25 SLE patients with biopsy-proven membranous lupus nephritis (MLN) were serologically analysed before beginning or intensifying immunosuppressive therapy. It could be shown that even at time of biopsy none of the MLN patients exhibited anti-PLA2R autoantibodies, whereas three patients with primary MN revealed high titers.2

Modified from: Gunnarsson et al., Am J Kidney Dis 59, 582-589 (2012)
Modified from: Gunnarsson et al., Am J Kidney Dis 59, 582-589 (2012)

Nonetheless, a few cases of secondary MN have been reported in which anti-PLA2R were detected. Based on several studies, Ronco and Debiec calculated a prevalence of anti-PLA2R of 5-30 % in selected forms of secondary MN.3

 


Modified from: Ronco & Debiec, Nat Rev Nephr 8, 203-213 (2012)
Modified from: Ronco & Debiec, Nat Rev Nephr 8, 203-213 (2012)

Still, a coincidence of primary MN with an additional disease cannot be ruled out from these data. Moreover, the data were determined using non-standardised assays.


In contrast, two studies which used commercial and standardised assays from EUROIMMUN yielded the following results: All patients with secondary MN were found to be negative for anti-PLA2R autoantibodies using either Anti-PLA2R IIFT (IgG) (n=17) or Anti-PLA2R ELISA (IgG) (n=27).4,5 Therefore, anti-PLA2R autoantibodies can be considered as very specific markers for primary MN and are ideally suited for differentiation of primary from secondary MN.