Discriminating between cases of primary and secondary Membranous Nephropathy (MN)

There has been a breakthrough in diagnosis and management of primary MN in the last few years now that it is possible to measure anti-PLA2R autoantibodies in serum of 70% of cases. In some early cases, it appears that the kidney can adsorb all of the circulating anti-PLA2R so that it is possible to find PLA2R antigen in the kidney immune complexes, when the patient is apparently serum antibody negative.

So, in addition to the ELISA that we have developed to detect circulating anti-PLA2R, we need to establish a validated immunostaining method for detecting the PLA2R antigen in the kidney biopsy. There are no antibodies to the full length PLA2R antigen and the only available antibody binds to the same part of the antigen as do the endogenous autoantibodies. This makes it unreliable as a diagnostic reagent when the human antibodies have bound to the antigen in immune complexes.

We believe that this validated immunostaining test for PLA2R antigen in the biopsy will differentiate primary and secondary MN cases. Primary cases will be antibody seropositive/ biopsy antigen positive and secondary cases (tumour) will be antibody seronegative/biopsy antigen negative). Improving the sensitivity and specificity for an early correct diagnosis of primary and secondary MN will improve the likely chance of a cure of the malignancy associated with secondary MN.