Background/Purpose:

Recently phospholipase A2 receptor 1 (PLA2R1) has been found to be the antigenic target for primary membranous nephropathy (pMN) (1). Circulating anti-PLA2R1 autoantibody can be used as a marker for diagnosis and monitoring of pMN, and due to their high specificity, PLA2R1 antibody detection is useful in discriminating patients with pMN from those with secondary MN. A recent review calculated an overall PLA2R1 prevalence of 4.4% in membranous lupus nephritis (mLN)(2). PLA2R1 has  been described in mLN patients with Chinese origin but not in Caucasians, raising the possibility of ethnic differences (3).  We therefore sought to define the frequency of anti-PLA2R1 antibody in our ethnically diverse mLN population.

Methods:

This was a retrospective analysis of blood samples taken from lupus patients meeting ACR classification criteria with biopsy proven pure WHO class V or overlap (class III/V or IV/V) LN. ELISA was used to detect the presence or absence of the PLA2R1 antibody.  Urinary protein : creatinine ratio (PCR) , erythrocyte sedimentation rate (ESR), dsDNA  and complements were measured.

Results:

38 patients with biopsy proven mLN were tested for PLA2R1 antibody. There were 17 (44.7%) South-Asian, 14 (36.8%) Afro-Caribbean, 5 (13.2%) Caucasian, 1 South-East Asian and 1 Mixed. 5 of the 38 patients were Male (F:M ratio 6.6:1), and age range was from 21-60. 60% of the total group had significant proteinuria (uPCR>50), of whom 9 (23.7%) were in the nephrotic range. Median PCR was 91. 11 (29%) had active renal disease at the time of measurement of PLA2-R1 antibody based on significant increase of proteinuria warranting consideration of escalation of immunosuppression.  13 (39%) patients had elevated dsDNA titres, 8 (21%) patients had low complement levels and 18 (47%) patients had raised ESR >20. All patients were negative for the PLA2R1 antibody.

Conclusion:

Our results support the high reported specificity for PLA2R1 antibodies for pMN. The previously reported finding of PLA2R1 antibodies in SLE is most likely due to a chance co-occurrence of primary MN rather than ethnic differences.  Since PLA2R1 has therapeutic and prognostic implications in pMN, its measurement should be considered in proteinuric lupus patients who are older and male since this is the group most likely to present with pMN.

(1)    Beck et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy N Engl J Med 361, 11-21 (2009)

(2)    Ronco P , Debiec Pathogenesis of membranous nephropathy: recent advances and future challenges H Nat Rev Nephr 8, 203-213 (2012)

(3)    Qin W et al . Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy. JASN  2011. 22(6) 1137-43

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/phospholipase-a2-receptor-1-antibody-in-membranous-lupus-nephritis/