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

• Published in: Kidney international Vol. 92; no. 1; p. 227
• Main Authors: Rosenzwajg, Michelle, Languille, Eva, Debiec, Hanna, Hygino, Joana, Dahan, Karine, Simon, Tabassome, Klatzmann, David, Ronco, Pierre
• Format: Journal Article
• Language: English
• Published: United States 01-07-2017
• Subjects: Adult; Aged; Autoantibodies - blood; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Biomarkers - blood; CD4 Lymphocyte Count; CD56 Antigen - blood; Female; Glomerulonephritis, Membranous - blood; Glomerulonephritis, Membranous - diagnosis; Glomerulonephritis, Membranous - drug therapy; Glomerulonephritis, Membranous - immunology; GPI-Linked Proteins - blood; Humans; Immunophenotyping; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Interleukin-2 Receptor alpha Subunit - blood; Interleukin-5 - blood; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Male; Middle Aged; Paris; Phenotype; Predictive Value of Tests; Receptors, IgG - blood; Rituximab - adverse effects; Rituximab - therapeutic use; Severity of Illness Index; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; regulatory T cells; natural killer cells; TNF-α; memory B cells; membranous nephropathy; rituximab
• ISSN: 1523-1755
• DOI: 10.1016/j.kint.2017.01.012

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 CD56
CD16
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 CD56
CD16
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.