Killer-cell immunoglobulin-like receptor expression on lymphocyte subsets in multiple sclerosis patients treated with interferon-β: evaluation as biomarkers for clinical response

CNS Drugs. 2014 Jun;28(6):559-70. doi: 10.1007/s40263-014-0153-7.

Abstract

Background: Both the adaptative and the innate immune systems interplay in multiple sclerosis (MS) pathogeny. Killer-cell immunoglobulin-like receptors (KIRs) are key regulators of the immune response, with activating and inhibitory isoforms.

Objective: In this study we analysed whether the expression of KIR isoforms is implicated in MS pathogenesis and in the therapeutic response to interferon (IFN)-β.

Methods: Peripheral blood samples were collected from 78 IFN-β-treated MS patients and 46 healthy controls (HC). KIR expression was evaluated by flow cytometry on natural killer (NK) and T cells.

Results: The expression of KIRs on NK cells and T lymphocytes did not differ between MS patients and HC. IFN-β therapy decreased the expression of KIR2DL1/2DS1 and increased that of KIR2DL2/3 on NK cells. This therapy also reduced KIR2DL1/2DS1, KIR2DL2/2DL3 and KIR3DL2 expression on CD8(+) T cells. The baseline evaluation of the percentage of circulating CD16(+) NK cells was predictive of the clinical response to IFN-β; however, response to this therapy did not appear related to KIR expression.

Conclusions: This study shows that expression of KIR isoforms on NK and T lymphocytes correlated in different ways with IFN-β therapy, suggesting that KIR dynamics may be associated with the pathways involved in the mechanisms of action of IFN-β.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Adult
  • Biomarkers / blood
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Interferon-beta / administration & dosage
  • Interferon-beta / therapeutic use*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Predictive Value of Tests
  • Receptors, IgG / immunology
  • Receptors, KIR / genetics*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunologic Factors
  • Receptors, IgG
  • Receptors, KIR
  • Interferon-beta