Circulating Anti-PLA2R Autoantibodies to Monitor Immunological Activity in Membranous Nephropathy

Cravedi, Paolo; Ruggenenti, Piero

doi:10.1681/asn.2011060610

Cited by 25 publications

(24 citation statements)

References 20 publications

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“…corroborated the hypothesis of a cause and effect relationship between the production of nephritogenic antibodies by autoreactive B lymphocytes and disease activity. [34][35][36][37][38] An additional unique aspect of our study, compared with previous trials in IMN, is that a subgroup of patients had their GFR measured by a gold standard technique. 39 This allowed discovering that complete remission was associated with a significant improvement of the GFR that approximated 13 ml/min per 1.73 m 2 versus baseline.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in Idiopathic Membranous Nephropathy

Ruggenenti

Cravedi

Chianca

et al. 2012

Journal of the American Society of Nephrology

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271

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Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria ,0.3 g/24 h and partial remission as persistent proteinuria ,3 g/24 h, each also having .50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m 2 among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.

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Section: Discussionmentioning

confidence: 99%

Rituximab in Idiopathic Membranous Nephropathy

Ruggenenti

Cravedi

Chianca

et al. 2012

Journal of the American Society of Nephrology

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271

213

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“…12 There is a suggestion that anti-PLA2R1 antibody levels correlate with disease activity and/or with response to treatment. 13 Testing for this auto-antibody therefore shows promise, not only in diagnosis of IMN but also in monitoring. Commercial assays for anti-PLA2R1 are now available.…”

Section: Recent Advances In Understandingmentioning

confidence: 99%

Membranous nephropathy

Mathieson

2012

Clinical Medicine

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“…The landmark discovery that circulating anti-PLA2 2 R autoantibodies are almost exclusively specific to patients with primary MN offered clinicians and scientists a powerful tool to differentiate primary from secondary forms and monitor disease activity and response to therapy. 10 Finding that some cases of primary MN tend to cluster in families has been taken to suggest that genetic factors may contribute to the production of anti-PLA 2 R autoantibodies. This hypothesis was recently corroborated by genome-wide association studies revealing significant associations of the 6p21 HLA-DQA1 and 2q24 PLA2R1 loci with primary MN in patients of white ancestry 11 and in ethnically distant populations from Europe 12 and Asia.…”

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confidence: 99%

Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy

Ruggenenti

Dębiec

Ruggiero

et al. 2015

Journal of the American Society of Nephrology

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309

255

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Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A 2 receptor (anti-PLA 2 R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m 2 ) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximabtreated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA 2 R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA 2 R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P,0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA 2 R antibody depletion. On average, 50% anti-PLA 2 R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P,0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA 2 R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.

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Circulating Anti-PLA2R Autoantibodies to Monitor Immunological Activity in Membranous Nephropathy

Cited by 25 publications

References 20 publications

Rituximab in Idiopathic Membranous Nephropathy

Rituximab in Idiopathic Membranous Nephropathy

Membranous nephropathy

Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy

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