Immunomodulation of inflammatory leukocyte markers during intravenous immunoglobulin treatment associated with clinical efficacy in chronic inflammatory demyelinating polyradiculoneuropathy

Wayne B. Dyer, Joanne C.G. Tan, Timothy Day, Lynette Kiers, Matthew C. Kiernan, Con Yiannikas, Stephen Reddel, Karl Ng, Phillip Mondy, Peta M. Dennington, Melinda M. Dean, Halina M. Trist, Cristobal dos Remedios, P.Mark Hogarth, Steve Vucic, David O. Irving

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: The objective of the study was to profile leukocyte markers modulated during intravenous immunoglobulin (IVIg) treatment, and to identify markers and immune pathways associated with clinical efficacy of IVIg for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with potential for monitoring treatment efficacy. Methods: Response to IVIg treatment in newly diagnosed IVIg-naïve and established IVIg-experienced patients was assessed by changes in expression of inflammatory leukocyte markers by flow cytometry. The adjusted INCAT disability and Medical Research Council sum scores defined clinical response. Results: Intravenous immunoglobulin modulated immunopathogenic pathways associated with inflammatory disease in CIDP. Leukocyte markers of clinical efficacy included reduced CD185+ follicular helper T cells, increased regulatory markers (CD23 and CD72) on B cells, and reduction in the circulating inflammatory CD16+ myeloid dendritic cell (mDC) population and concomitant increase in CD62L and CD195 defining a less inflammatory lymphoid homing mDC phenotype. A decline in inflammatory CD16+ dendritic cells was associated with clinical improvement or stability, and correlated with magnitude of improvement in neurological assessment scores, but did not predict relapse. IVIg also induced a nonspecific improvement in regulatory and reduced inflammatory markers not associated with clinical response. Conclusions: Clinically effective IVIg modulated inflammatory and regulatory pathways associated with ongoing control or resolution of CIDP disease. Some of these markers have potential for monitoring outcome.

Original languageEnglish
Article numbere00516
Number of pages11
JournalBrain and Behavior
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 2016
Externally publishedYes

Keywords

  • autoimmune neuropathies
  • chronic inflammatory demyelinating polyradiculoneuropathy
  • dendritic cells
  • disease pathways
  • Fc-gamma receptors
  • immunophenotyping
  • intravenous immunoglobulin G

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