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

Michelle Rosenzwajg (1, 2) , Eva Languille (3) , Hanna Debiec (3) , Joana Hygino (1) , Karine Dahan (4) , Tabassome Simon (5) , David Klatzmann (1, 2) , Pierre Ronco (3, 4)

1 CHU Pitié-Salpêtrière [AP-HP]
2 I3 - Immunologie - Immunopathologie - Immunothérapie
3 Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation
4 CHU Tenon [AP-HP]
5 CHU Saint-Antoine [AP-HP]

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 CD56brightCD16-/lo 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 CD56brightCD16-/lo 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.

Keywords: memory B cells; natural killer cells; regulatory T cells; membranous nephropathy; rituximab; TNF-α

Domains: Urology and Nephrology; Immunotherapy

Michelle Rosenzwajg, Eva Languille, Hanna Debiec, Joana Hygino, Karine Dahan, et al.. B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab. Kidney International, 2017, pp.227-237. ⟨10.1016/j.kint.2017.01.012⟩. ⟨hal-01493184⟩