B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Abstract

Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56CD16 NK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56CD16 NK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.

Primary Membranous Nephropathy as a Model of Autoimmune Disease

“…As the technology evolves, flow cytometry is becoming an ever more powerful tool for the study of the immune system. A recent study using patients enrolled in the GEMRITUX trial showed that patients had lower proportions of IgD− and IgD+ memory B cells, T Regs and a higher proportion of naïve B cells at baseline compared to healthy donors [71]. In this study by Rosenzwajg et al, patients who responded to treatment were observed to have a lower proportion of T Regs at baseline compared to those who did not respond to treatment.…”

Variation of Peripheral Th17/Treg Imbalance in Patients with Idiopathic Membranous Nephropathy after Cyclosporin A Treatment: A Prognostic Marker of Idiopathic Membranous Nephropathy

“…However, we did not have further research on why CSA treatment of IMN was unresponsive. CsA does not prevent continuing autoantibody formation, production and deposition of IgG4 in the glomeruli may promote the development of MN, 16 but still need larger samples, a long-term follow-up to confirm.…”

“…After rituximab monoclonal antibody therapy, peripheral Treg% is elevated, which is intimately correlated with clinical efficacy. 6 Nevertheless, existence of Th17/Treg imbalance in IMN patients, its correlation with the progression and clinical prognosis of IMN patients has not yet been thoroughly investigated.…”

Clinical value of renal phospholipase A2 receptor deposit in the prognosis evaluation and treatment options of idiopathic membranous nephropathy: A retrospective cohort study

“…Univariate COX regression analysis showed that positive renal PLA2R antigen was risk factor for not achieving sponta- 64 41 27 12 10 6 3 3 1 13 13 12 4 3 3 3 3 3 3 1 Log-rank p=0.012 F I G U R E 3 Kaplan-Meier analysis of spontaneous remission in patients with positive and negative phospholipase A2 receptor (PLA2R) antigen deposit. The numbers of at-risk patients at selected time points (3,6,9,12,15,18,21,24,27 and 30 months) were indicated below the plot. Log-rank method was used to evaluate the significance of differences serum albumin and proteinuria, positive renal PLA2R antigen was still an independent risk factor for not achieving spontaneous remission in IMN patients (HR: 2.927; 95% CI: 1.270 to 6.743; P = .012) ( Table 3).…”