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Background and Aims Studies in lupus nephritis (LN) have shown impairment in both T regulatory (Treg) number and function. However, the data on B regulatory (Breg) is limited in LN. Our objective was to study Breg and Treg populations in newly diagnosed treatment naïve LN and study their change after initiation of immunosuppression. Method Study included 25 patients of newly diagnosed LN of Class III (+V), IV (+V), V and 10 healthy controls (HC). Immunophenotyping was performed for peripheral blood mononuclear cell (PBMCs) samples using fluorochrome labelled monoclonal antibodies for Tregs (CD3+CD4+CD25hiCD127loFoxP3+) and Bregs (CD19+CD5+CD1dhi IL-10+). The cells were expressed as percentage of T and B cells. Each lymphocyte population was analysed at baseline, 2 and 6 months after initiation of immunosuppression which was given as per unit protocol. Results Bregs were significantly decreased compared to HC at baseline (p=0.002). With immunosuppression, Bregs showed significant increase at 2 and 6 months (p=0.008) and from baseline to 6 months (p=0.005). Bregs in responders significantly increased from 2 to 6 months (p= 0.017) and from baseline to 6 month (p=0.020), while they did not in non-responders. Tregs did not differ significantly from HC and did not show significant increase at 2 and 6 months, in both responders and non-responders. Conclusion Breg population in newly diagnosed LN was significantly reduced and increased significantly with immunosuppression. Bregs had an association with renal remission. This underscores the potential role of Bregs in the pathophysiology of LN and their association with clinical response. This could aid in the design of new immunotherapies for treatment of lupus nephritis.

Background and Aims Different rituximab dosing schedules have been used to manage primary membranous nephropathy (PMN). Better response rate and toxicity needs to be balanced to arrive at correct dose. The dosing schedules in PMN as of now are an on the lines of the management of lymphoma or rheumatoid arthritis. In the current study, we report the 1-year outcome of patients treated with three dosing schedules of rituximab in PMN. Method The current report is a study of patient of PMN treated with three different dosing schedules of rituximab treatment. The study included PMN patients with nephrotic syndrome (proteinuria>3.5 g/day and serum albumin of < 3.5 g/dL). Patients with secondary membranous nephropathy and a history of prior exposure of immunosuppressive therapy in the last three months were excluded from the study. The three dosing schedules of rituximab were 1 g (on day 0,15) (regimen 1), 375 mg/m2 (weekly for four weeks) (regimen 2) or CD19 targeted rituximab therapy (375 mg/m2 as the initial dose and additional dose 100 mg, when the CD19 cell count was> 5/ul or >1%, done every month for 12 months) (regimen 3). Serum PLA2R autoantibodies were done before rituximab therapy and at six months of therapy initiation. Primary outcomes: Remission at the end of 12 months of therapy initiation. Secondary outcome: Complete remission (CR) and partial remission (PR), remission with different treatment schedules and adverse events. Definition: CR: reduction of proteinuria to 60 ml/min/1.73m2 and serum albumin > 3.5 g/dl. PR: reduction of proteinuria to 0.5–3.5 g/day and stable serum creatinine. A p-value of Results The study included 87 patients of PMN. The mean age of the patients was 33.36±15.38 (range 15-61) years. Thirty-two (36.4%) and 56 (63.6%) patients received rituximab as the first-line therapy and for relapsing/resistant disease, respectively. Forty, 15 and 33 patients received regimen 1, 2 and 3, respectively. The median proteinuria, serum albumin and creatinine at the baseline before rituximab therapy was 5.90 (IQR 4.20,9.75) gm, 2.50 (IQR 2.15,3.25) g/dl and 0.88 (IQR 0.77,1.09) mg/dl, respectively. At the end of 12 months of follow-up, 55 (56.8%) patients received remission. Nineteen (21.6%) and 32 (36.3%) patients achieved CR and PR, respectively. In regimen 1, 12 (30%) and 13 (32.5%) patients achieved CR and PR, respectively. In regimen 2, 2 (13.3%) and 5 (33.3%) patients achieved CR and PR, respectively. In regimen 3, 5 (15.6%) and 14 (43.7%) patients achieved CR and PR, respectively. One patient in the CD19 targeted therapy (regimen 3) was lost to follow-up after the 1st dose; all but one patient in the received regimen three as a second-line treatment. There was a significant association of anti-PLA2R to clinical response (p0.05). A total of 7 (7.9%) patients had severe adverse events, there was no difference in the 3 regimens. (p>0.05) The cumulative dose in regimen 3 was significantly less as compared to regimen 1 & 2 (p Conclusion Rituximab induces remission in two-thirds of the patients with PMN. There is no significant difference in the remission rates between different rituximab regimens. CD19 targeted therapy is equally effective with lower cumulative dose.

Background. The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding. Methods. We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2g/day for 6 months along with prednisolone at 0.5mg/kg/day for 2–3 months. Conventional therapy was prednisolone 1mg/kg/day for 3–6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio. Results. A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose. Conclusions. A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster andreducessteroidexposureinFSGSpatients.Studieswith more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.