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Neurology. 2014 Oct 21;83(17):1500-7. doi: 10.1212/WNL.0000000000000908. Epub 2014 Sep 24.

Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS.

Author information

1
From the Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, Departments of Neurology (A.K.H., D.N.I., B.M.S.), Biostatistics (L.W.), and Radiology (A.S.), University of Michigan, Ann Arbor; Neurology Service (B.M.S.), VA Ann Arbor Healthcare System, MI; Department of Statistics and Actuarial Science (P.H.), University of Waterloo, Canada; Department of Mathematics and Statistics (X.Z.), Bowling Green State University, OH; and Department of Imaging Sciences (S.E.), University of Rochester Medical Center, NY.
2
From the Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, Departments of Neurology (A.K.H., D.N.I., B.M.S.), Biostatistics (L.W.), and Radiology (A.S.), University of Michigan, Ann Arbor; Neurology Service (B.M.S.), VA Ann Arbor Healthcare System, MI; Department of Statistics and Actuarial Science (P.H.), University of Waterloo, Canada; Department of Mathematics and Statistics (X.Z.), Bowling Green State University, OH; and Department of Imaging Sciences (S.E.), University of Rochester Medical Center, NY. bmsegal@umich.edu.

Abstract

OBJECTIVE:

In the current exploratory study, we longitudinally measured immune parameters in the blood of individuals with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and investigated their relationship to disease duration and clinical and radiologic measures of CNS injury.

METHODS:

Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from subjects with RRMS, SPMS, and from healthy controls on a monthly basis over the course of 1 year. MRI and Expanded Disability Status Scale evaluations were performed serially. PBMCs were analyzed by enzyme-linked immunosorbent spot assay to enumerate myelin basic protein-specific interleukin (IL)-17- and interferon (IFN)-γ-producing cells. Plasma concentrations of proinflammatory factors were measured using customized Luminex panels.

RESULTS:

Frequencies of myelin basic protein-specific IL-17- and IFN-γ-producing PBMCs were higher in individuals with RRMS and SPMS compared to healthy controls. Patients with SPMS expressed elevated levels of IL-17-inducible chemokines that activate and recruit myeloid cells. In the cohort of patients with SPMS without inflammatory activity, upregulation of myeloid-related factors correlated directly with MRI T2 lesion burden and inversely with brain parenchymal tissue volume.

CONCLUSIONS:

The results of this exploratory study raise the possibility that Th17 responses and IL-17-inducible myeloid factors are elevated during SPMS compared with RRMS, and correlate with lesion burden. Our data endorse further investigation of Th17- and myeloid-related factors as candidate therapeutic targets in SPMS.

PMID:
25253754
PMCID:
PMC4222856
DOI:
10.1212/WNL.0000000000000908
[Indexed for MEDLINE]
Free PMC Article

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