Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

PLoS One. 2016 Oct 6;11(10):e0164099. doi: 10.1371/journal.pone.0164099. eCollection 2016.

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker.

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Immunoglobulins, Intravenous / pharmacology*
  • Immunoglobulins, Intravenous / therapeutic use
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / blood
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred NOD
  • Neuritis / diagnostic imaging
  • Neuritis / drug therapy*
  • Neuritis / metabolism
  • Neuritis / pathology
  • Sural Nerve / diagnostic imaging
  • Sural Nerve / drug effects
  • Sural Nerve / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Immunoglobulins, Intravenous
  • Interleukin-17
  • Intercellular Adhesion Molecule-1

Grants and funding

G.M.z.H. was funded in part by grants from the Deutsche Forschungsgemeinschaft (DFG grant number ME4050/1-1), from the National Multiple Sclerosis Society (NMSS) (postdoctoral fellowship grant number FG 20118-A-1), from the Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen (MIWF NRW), and by a project grant from the Peripheral Nerve Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.