Effective treatment with intravenous immunoglobulins reduces autoreactive T-cell response in patients with CIDP

J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):686-91. doi: 10.1136/jnnp-2014-307708. Epub 2014 Jul 29.

Abstract

Objective: To investigate changes in autoreactive T-cell responses against PMP-22 and P2 antigen as well as a T-cell memory repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) induced by repeated intravenous immunoglobulin (IVIg) treatment.

Methods: In an observational trial, we prepared cryopreserved human peripheral blood monocytes from blood from 34 patients with CIDP (18 treatment naïve and 16 maintenance IVIg treatment) and from 14 healthy controls (non-immune neuropathy and healthy control). Treatment response was defined by clinical evaluation. The autoantigen-specific T-cell response was analysed by enzyme linked immunosorbent spot (ELISPOT) assay before IVIg start (baseline) and at follow-up. The T-cell memory subsets were analysed by using flow cytometric analysis.

Results: Myelin-derived P2-specific and PMP-22-specific IFN-γ producers were increased in IVIg responders compared with non-responders before treatment, which decreased by repeated IVIg infusion cycles. Treatment responders but not non-responders showed higher frequencies of CD4 T effector memory (TEM) and T central memory frequencies at baseline compared with maintenance IVIg treatment patients and controls. In addition, IVIg treatment was associated with a significant reduction in CD8 TEM at follow-up.

Conclusions: Our data demonstrate that immunomodulatory treatment with IVIgs on a long-term basis reduces the autoreactive T-cell response against PMP-22 and P2-antigens, which may be influenced by the altered maintenance of CD8 and CD4 effector/memory T-cell subsets towards a more anti-inflammatory immune status. Elevated PMP-22 and P2-specific T-cell responses may serve as predictors for treatment responsiveness to IVIgs warranting validation in larger studies.

Keywords: Neuropathy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Memory
  • Immunotherapy / methods*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Myelin Sheath / immunology
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / immunology*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / therapy*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Young Adult

Substances

  • Autoantigens
  • Immunoglobulins, Intravenous