B- And T-cell Subpopulations in Patients With Severe Idiopathic Membranous Nephropathy May Predict an Early Response to Rituximab

Kidney Int. 2017 Jul;92(1):227-237. doi: 10.1016/j.kint.2017.01.012. Epub 2017 Mar 15.

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

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • GPI-Linked Proteins / blood
  • Glomerulonephritis, Membranous / blood
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology
  • 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

Substances

  • Autoantibodies
  • Biomarkers
  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • IL2RA protein, human
  • IL5 protein, human
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-5
  • NCAM1 protein, human
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Rituximab