Individual natural data of participants with membranous nephropathy relapses. Supplemental Amount 1. to review two protocols of rituximab in two potential cohorts of anti-PLA2R1Cpositive sufferers. Materials and Strategies Study Style and Patient Populace Patients were enrolled after signing informed consent from the two prospective studies. The NICE cohort recruited consecutive participants with primary membranous nephropathy in the Department of Nephrology at Pasteur Hospital in Nice (Clinicaltrials.gov identifier “type”:”clinical-trial”,”attrs”:”text”:”NCT02199145″,”term_id”:”NCT02199145″NCT02199145), testing epitope profile at diagnosis to predict the need of immunosuppressive therapy (rituximab); only participants recruited in Nice Hospital, treated by rituximab and followed at least 1 year were included in this study. The GEMRITUX cohort is usually a part of a French multicenter, randomized, controlled trial (Clinicaltrials.gov identifier “type”:”clinical-trial”,”attrs”:”text”:”NCT01508468″,”term_id”:”NCT01508468″NCT01508468) testing rituximab added to antiproteinuric therapy against antiproteinuric therapy alone (22); only participants with anti-PLA2R1 antibodies treated with rituximab were included in this study. The inclusion criteria were (value 0.05 indicated statistical significance. Analyses were performed using SAS software v.9.3 (SAS Institute, Cary, NC). Results Comparison of the NICE and GEMRITUX Cohorts at Baseline The NICE cohort included 28 consecutive PLA2R1-positive participants who received two 1-g infusions of rituximab at 2-week intervals after 6 months of symptomatic treatment, or earlier in the case of Methyllycaconitine citrate acute complications according to the KDIGO guidelines. Seven participants were treated after 6 months of symptomatic treatment: two presented with thromboembolic complications at diagnosis and five participants developed progressive kidney failure. The GEMRITUX cohort included 27 PLA2R1-positive participants from the French GEMRITUX clinical trial (22) who were given two 375 mg/m2 infusions of rituximab at 1-week intervals at least 6 months after kidney biopsy. Participants baseline characteristics were similar, apart from an older age in the NICE cohort (63 [interquartile range (IQR), 51C71] versus 51 [IQR, 40C63] years; Valuesvalue for remission was Value(25) have shown that low-dose rituximab can reduce cost, whereas other groups (24,27) have found that low-dose regimens are poorly effective. Our results suggest that low doses may delay remission even if B cell depletion is usually achieved. Methyllycaconitine citrate Absence of remission at last follow-up was associated with lower residual Methyllycaconitine citrate serum rituximab levels, higher CD19 count, and higher anti-PLA2R1 antibody levels at month 3. These findings make a case for the use of the NICE regimen, which was also used in the Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR), instead of the GEMRITUX regimen. They also suggest that the dose of rituximab might be insufficient in patients with heavy proteinuria in whom we have recently shown that reinfusion of rituximab could induce remission in patients that were considered refractory to Methyllycaconitine citrate rituximab (35). The second aim was to identify factors associated with remission at month 6 and last follow-up in the two combined cohorts. We confirmed that the absence of spreading at baseline was associated with higher rate of clinical remission (23). We found that the percentage of epitope spreaders tended to be lower at month 6 with the NICE protocol, which suggests that high-dose rituximab may reverse spreading. Further studies are needed to determine if this improves outcome as compared with patients that fail to experience spreading reversal. A TRIB3 combined analysis of rituximab protocol and spreading suggested that this NICE protocol blunted the effects of spreading on clinical remission at last follow-up. As long as epitope spreading is not routinely available, we propose that patients with anti-PLA2R1 titer 321 RU/ml (using Euroimmun ELISA) should receive high-dose rituximab. We showed that in patients with anti-PLA2R1 titer 321 RU/ml, 95% are spreaders. We previously exhibited in the GEMRITUX cohort.