In Vitro Study of the Efficacy of Different Immunomodulators on the Th17/Treg Balance in a Cohort of Relapsed Membranous Nephropathy

Membranous Nephropathy (MN) is a rare autoimmune renal disease and the first cause of nephrotic syndrome in adults. In one third of cases, it progresses to end-stage renal failure. Rituximab has shown very good efficacy (60-80%) and excellent safety in this indication. However, one third of MN patients relapse after a course of rituximab, raising the question of maintenance treatment or repeated courses of rituximab whose long-term impact is unknown.

The investigators studied the cytokine profile of MN patients and demonstrated, after non-specific stimulation of innate immunity cells and T cells, a Th17 profile (increased levels of interleukin-6 (Il-6) and interleukin-17A (Il-17A) compared to healthy subjects), and inhibition of the Th1 (decreased IL-12p70 and Interferon-γ (IFN-γ)) and T regulatory T reg pathways (decreased IL-10) (doi: 10. 3389/fimmu.2020.574997).

Th17 cells and Treg cells with interconnected development have opposite roles. Th17 cells induce inflammation to initiate a reaction against a pathogen, while Treg cells control an inflammatory reaction.

The investigators showed that high Il-17A levels were associated with a risk of thrombotic events (p = 0.03) and relapse (p = 0.0006). A patient with an IL-17A level > 73 pg/ml had a 10.5-fold increased risk of relapse.

Rituximab-induced remission leads to an increase in Treg and Th1 pathway cytokines but has no impact on IL-17A production, which remains important even in remission.