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

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

doi:10.1002/brb3.516

Abstract

ObjectiveThe 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.MethodsResponse 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.ResultsIntravenous 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.ConclusionsClinically 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.

Highlights

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immunologically heterogeneous autoimmune inflammatory disease resulting in peripheral nerve demyelination, causing profound disability in more than 50% of cases (Franssen & Straver, 2014; Mathey et al, 2015)
This study confirmed some of the known immunomodulatory action of intravenous immunoglobulin (IVIg) on disease pathways of inflammatory neuropathies, and identified markers associated with clinical outcome
Changes in disease pathways associated with clinical efficacy included reduced capacity for autoantibody production associated with decreased follicular helper T cells and increased expression of regulatory and tolerance markers on B cells

Summary

| INTRODUCTION

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immunologically heterogeneous autoimmune inflammatory disease resulting in peripheral nerve demyelination, causing profound disability in more than 50% of cases (Franssen & Straver, 2014; Mathey et al, 2015). High-dose intravenous immunoglobulin (IVIg), with a superior safety profile to steroids (Dalakas, 2012), is a preferred first-line treatment with established evidence of efficacy (Hughes et al, 2008). There are no definitive strategies to predict the optimal IVIg dose nor the response to treatment, suggesting frequent monitoring is required to establish optimal treatment in new patients. Immunomodulatory effects of IVIg have been observed across diverse leukocyte populations, including immunopathogenic disease pathways characteristic of CIDP (Dalakas, 2011; Ephrem et al, 2005; Mathey & Pollard, 2013; Mathey et al, 2015). The data provide evidence that immune phenotyping before and after IVIg treatment can be used to distinguish responders from nonresponders, and suggest targeting- specific markers and pathways for monitoring clinical response to IVIg in CIDP is feasible

| METHODS

Findings

| DISCUSSION