The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy

Eur J Neurol. 2011 Jun;18(6):919-24. doi: 10.1111/j.1468-1331.2010.03333.x. Epub 2011 Jan 11.

Abstract

Background and purpose: High-dose intravenous immunoglobulin (IVIg) is an established treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although Fc receptors on natural killer cells have been suggested as a target for IVIg, the pharmacological effects are not yet clarified. We hypothesize that IVIg therapy, dependent on the plasma IgG level, suppresses the cytotoxic capacity by a reduction in numbers of NK cells and their Fc receptor CD16.

Patients and methods: Ten consecutive patients with CIDP in maintenance therapy with IVIg were studied before and immediately after the infusion of 0.7-2.0 g/kg IVIg. Peripheral blood mononuclear cell samples from these patients were analyzed immediately after isolation using flow cytometry and cytotoxicity assays.

Results: We found that following IVIg treatment, the cytotoxic activity of NK cells in CIDP patients was suppressed, partly caused by a dose-dependent decline in the number of circulating NK cells. In addition, a dose-dependent blockage of CD16 occurred.

Conclusions: The study implies that IVIg infusion induces a substantial decline in the number of peripheral NK cells and a suppression of NK-cell-mediated cytotoxicity. We propose that these impairments of the NK cells contribute to the therapeutic effect of IVIg in CIDP.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cytotoxicity Tests, Immunologic
  • Dose-Response Relationship, Immunologic
  • Female
  • GPI-Linked Proteins / drug effects
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulins, Intravenous / administration & dosage*
  • Immunoglobulins, Intravenous / blood
  • Immunosuppressive Agents / pharmacology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / drug therapy*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / immunology*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / physiopathology
  • Receptors, Fc / metabolism*
  • Receptors, Fc / physiology
  • Receptors, IgG / drug effects
  • Receptors, IgG / metabolism
  • Young Adult

Substances

  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Receptors, Fc
  • Receptors, IgG