Antiphospholipase 2 receptor antibody levels to predict complete spontaneous remission in primary membranous nephropathy

Abstract

BackgroundM-type phospholipase A2 receptor (APLA2R) is considered the major antigen involved in the pathogenesis of adult primary membranous nephropathy (MN), which is the leading cause of non-diabetic nephrotic syndrome. Antibodies to this antigen have been proved to be an excellent biomarker of disease activity in primary MN. In fact, preliminary data suggest that the higher the antibody level the more proteinuria, and that a decrease in antibody level precedes the remission of proteinuria, but more solid evidence is needed.MethodsThe present work aims to characterize the predictive value of the level of antibodies against PLA2R as a biomarker of disease course and treatment response in a well-defined cohort of 62 patients from University Hospitals Clinic of Barcelona and Josep Trueta in Girona. The primary outcome was the appearance of a spontaneous complete remission (CR), defined as induction of a CR without the use of immunosuppressive agents.ResultsIn common with other reports, this work confirms that spontaneous CR is more frequent in patients with low titre of APLA2R at diagnosis, but strikingly, in this cohort we found that spontaneous CR was achieved in patients with APLA2R levels <40 UI/mL. Furthermore, spontaneous CR were less frequently observed in patients with proteinuria >8 g/day.ConclusionsIn conclusion, these findings point out the important role of APLA2R as a tool to predict the disease course and establish personalized therapeutic options at the moment of diagnosis of primary MN. Specifically, patients with low titre of APLA2R (<40 UI/mL) and proteinuria <4/day could obtain benefit of a longer period of follow-up with conservative treatment after diagnosis.

RETRACTED: Role of Serum and Urine Biomarkers (PLA2R and THSD7A) in Diagnosis, Monitoring and Prognostication of Primary Membranous Glomerulonephritis

“…Anti-PLA 2 R Ab as a Prognostic Biomarker for Primary MGN An elevated anti-PLA 2 R Ab titre is associated with poor prognosis and increased risk of progression to ESRD [9] or post kidney transplantation failure [24][25][26] whereas low anti-PLA 2 R Ab titre is associated with spontaneous remission [21,[27][28][29]. Therefore, the low prevalence of anti-PLA 2 R Ab at the end of follow-up in this study demonstrated that anti-PLA 2 R Ab is a prognostic biomarker for primary MGN as against UPCr Index level, which showed fewer subjects achieving remission at the end of follow-up.…”

Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody

“…Furthermore, in the positive group, patients with a low titer had low 24-hour proteinuria levels, high albumin levels, mild pathological damage, and higher remission rates than those with a high antibody titer, thus suggesting that the patients with low antibody titers were more likely to achieve clinical remission. Rodas et al (2019) found that spontaneous CR did not occur in patients with PLA2R levels >40 IU/mL and was less frequently observed in patients with a proteinuria level >8 g/day. Furthermore, patients with high antibody levels had a higher risk of developing ESRD.…”

Peer Review #3 of "Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody (v0.1)"

“…Furthermore, in the positive group, patients with a low titer had low 24-hour proteinuria levels, high albumin levels, mild pathological damage, and higher remission rates than those with a high antibody titer, thus suggesting that the patients with low antibody titers were more likely to achieve clinical remission. Lida M Rodas et al (Rodas et al 2019) found that spontaneous CR did not occur in patients with PLA2R levels >40 IU/mL and was less frequently observed in patients with a proteinuria level >8 g/day. Furthermore, patients with high antibody levels had a higher risk of developing ESRD.…”