Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases

Abstract

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Receptor autoimmunity: diagnostic and therapeutic implications

“…IgG4 anti-PLAR antibodies are present in 50-80% of subjects with IMN [50,51] and virtually absent in secondary forms of IMN and other glomerular diseases [52]. Recently several new commercial immunoassays have been introduced with different assay formats; currently, CBA-IFI, ELISA and MBA-FIA methods are available in clinical practice and the serology quantitative approach is the cornerstone of the diagnosis, differential diagnosis, prognostic evaluation of activity, prediction of remission, and monitoring of post-transplant recurrence of the disease [53][54][55][56][57].…”

Clinical value of a serum anti-PLA2R antibody in the diagnosis and monitoring of primary membranous nephropathy in adults

“…The serum PLA2R antibody has diagnostic specificity and can be used to distinguish between PMN and other glomerular diseases. 6 It has been reported in People's Republic of China and other countries that serum anti-PLA2R antibody levels are associated with urinary protein levels, disease activity, improvement rate, recurrence, and drug resistance, etc. [7][8][9] This study analyzed the positive rate of serum anti-PLA2R antibodies among the PMN group, the SMN group, and non-MN group; quantitative changes in serum anti-PLA2R antibody levels before and after treatment were measured.…”

Membranous or membranous‐like GN: A case report of massive proteinuria, positive serum with negative PLA2R on biopsy

“…High titers are correlated to low risk of spontaneous remission and higher risk of the emergence of nephrotic syndrome in non‐nephrotic patients. Diagnostic sensitivity of anti‐PLA2R antibodies was found to be 70.6%, and diagnostic specificity of anti‐PLA2R antibody vs normal and pathological controls was 100% and 94.6%, respectively, as per Radice et al7 In 2013, examining 165 biopsies of primary and secondary membranous, Larsen et al8 reported sensitivity of 75% and a specificity of 83% for primary membranous glomerulopathy on PLA2R staining. Other causes of positive PLA2R biopsy staining were found to have hepatitis C, sarcoidosis (75%), and neoplasm (25%).…”