title: Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS.
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.
authors.affiliation: 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.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Huber
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Peisong
authors.initials: P
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Sven
authors.initials: S
authors.lastname: Ekholm
authors.affiliation: 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.
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: 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.
authors.forename: David N
authors.initials: DN
authors.lastname: Irani
authors.affiliation: 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.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053759:Interleukin-23 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood* / Q000473:pathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood; D004676:Myelin Basic Protein / Q000097:blood*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D004676:Myelin Basic Protein; D007371:Interferon-gamma