. 2023 Feb 22;18(4):533–548. doi: 10.2215/CJN.08570722

Table 1.

Summary of immunological modifications induced by rituximab therapy and relationship with disease relapse in childhood idiopathic nephrotic syndrome

Study	Study Design	Study Population	No. of Patients Analyzed	No. of Rituximab Courses	Rituximab Regimen per Course, mg/m²	Maintenance Immunosuppression	Immune Cells	Findings
Colucci et al.,¹⁸ 2016	Retrospective cohort study	FRNS/SDNS	28	1	375 × 1 (n=24) 375 × 2 (n=4)	Steroid MMF CNI For more than 3 months	B cells T cells	Complete depletion of total CD19⁺, transitional, mature-naive, and memory B-cell subsets, which started to reappear at 6 months; normalization of total CD19⁺, transitional, mature-naive B cells at 12 months; significant reduction of memory B-cell subsets at 12 months. A delayed recovery of total memory B cells and in particular of switched memory B cells was associated with a reduced risk of relapse. No association with relapse was found for the other B-cell subsets. No modification in total CD3⁺ T cells; normalization of the initially low CD4⁺/CD8⁺ T-cell ratio at 12 months. No association with relapse.
Chan et al.,¹⁹ 2016	Cohort study	SDNS (n=4) SRNS (n=18)	22	1	375 × 2 (n=10) 375 × 4 (n=12)	Steroid and CNI for <3 months MMF for more than 3 months	B cells T cells	Total CD19⁺ B cells started to reappear at 7 months. No association with relapse. At baseline, ex vivo activated T cells (CD154⁺CD4⁺CD3⁺, IFNγ⁺CD3⁺, IL-2⁺CD3⁺) were lower in responders compared with nonresponders; at 6 months, recovery of all three activated T-cell subsets was observed in responders and no modification was induced in nonresponders.
Bhatia et al.,¹⁴ 2018	Cohort study	SDNS	18	1	375 × 2 (n=18)	Steroid Tapered in 3–5 months	B cells T cells	Complete depletion of total CD19⁺ B cells in 16/18 patients, which started to reappear at 6 months. An earlier recovery of total CD19⁺ B cells and total memory B cells was associated with relapse. Reduction of Th17 and Th2 cells; increase of regulatory T cells. At relapse, patients had higher Th17 and Th2 cells and lower regulatory T cells. No modification of Th1 cells.
Boumediene et al.,¹⁵ 2018	Double-blind RCT	CNI- or MMF-dependent FRNS/SDNS	23	1	375 × 2 (n=10) Placebo (n=13)	Steroid MMF CNI For <3 months	B cells T cells	Not evaluated. No modification of total CD3⁺ T cells and of CD4⁺ and CD8⁺ T cells; reduction of T follicular helper cells and invariant natural killer T cells, associated with remission; increase of regulatory T cells. At relapse, patients had lower regulatory T cells.
Fribourg et al.,²⁰ 2021	Cohort study	CNI-dependent SDNS	30	1	375 × 1 (n=15) Ofatumumab 1.50 g/1.73 m² × 1 (n=15)	Steroid CNI For < 3 months	B cells T cells Innate immune cells	Total CD19⁺, transitional, naive, regulatory, antibody-secreting and memory B-cell subsets were significantly reduced after 3–7 months. An earlier recovery of switched B-cell subsets was associated with relapse. Reduction of Th17 and T follicular helper cells. No modification of Th1 or regulatory T cells. No association with relapse. No significant modification. No association with relapse.
Ravani et al.,¹⁶ 2021	Open-label, RCT	CNI-dependent SDNS	69^a	1	375 × 1 (n=33) Ofatumumab 1.50 g/1.73 m² × 1 (n=36)	Steroid MMF CNI For <3 months	B cells	Complete depletion of total CD19⁺, transitional, mature-naive, total memory, IgM memory, switched memory B cells and plasmablasts at 1 month, which started to reappear at 3 months in the rituximab arm and at 6 months in the ofatumumab arm; normalization of total CD19⁺, transitional, mature-naive B cells and plasmablasts at 12 months; significant reduction of memory B-cell subsets at 12 months. The transient more prolonged B-cell depletion with ofatumumab compared with rituximab did not modify the incidence of relapse at 12 and at 24 months.
							T cells	Transient increase of total CD3⁺ T cells at 1–3 months, with normalization at 12 months; regulatory T cells started to increase at 1–3 months and were still significantly higher at 12 months. Association with relapse was not evaluated.
							Innate immune cells	Transient increase of total CD56⁺ natural killer cells at 1–3 months, with normalization at 12 months. Association with relapse was not evaluated.

FRNS, frequently relapsing nephrotic syndrome; SDNS, steroid-dependent nephrotic syndrome; MMF, mycophenolate mofetil; CNI, calcineurin inhibitor; SRNS, steroid-resistant nephrotic syndrome; RCT, randomized controlled trial.

Data on immunological modifications were available for 69/140 enrolled patients.