title: Serum lipid antibodies are associated with cerebral tissue damage in multiple sclerosis.
abstract: OBJECTIVE
  To determine whether peripheral immune responses as measured by serum antigen arrays are linked to cerebral MRI measures of disease severity in multiple sclerosis (MS).
  
  
  METHODS
  In this cross-sectional study, serum samples were obtained from patients with relapsing-remitting MS (n = 21) and assayed using antigen arrays that contained 420 antigens including CNS-related autoantigens, lipids, and heat shock proteins. Normalized compartment-specific global brain volumes were obtained from 3-tesla MRI as surrogates of atrophy, including gray matter fraction (GMF), white matter fraction (WMF), and total brain parenchymal fraction (BPF). Total brain T2 hyperintense lesion volume (T2LV) was quantified from fluid-attenuated inversion recovery images.
  
  
  RESULTS
  We found serum antibody patterns uniquely correlated with BPF, GMF, WMF, and T2LV. Furthermore, we identified immune signatures linked to MRI markers of neurodegeneration (BPF, GMF, WMF) that differentiated those linked to T2LV. Each MRI measure was correlated with a specific set of antibodies. Strikingly, immunoglobulin G (IgG) antibodies to lipids were linked to brain MRI measures. Based on the association between IgG antibody reactivity and each unique MRI measure, we developed a lipid index. This comprised the reactivity directed against all of the lipids associated with each specific MRI measure. We validated these findings in an additional independent set of patients with MS (n = 14) and detected a similar trend for the correlations between BPF, GMF, and T2LV vs their respective lipid indexes.
  
  
  CONCLUSIONS
  We propose serum antibody repertoires that are associated with MRI measures of cerebral MS involvement. Such antibodies may serve as biomarkers for monitoring disease pathology and progression.
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ada
authors.initials: A
authors.lastname: Yeste
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Bonny
authors.initials: B
authors.lastname: Patel
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Subhash
authors.initials: S
authors.lastname: Tummala
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Roya
authors.initials: R
authors.lastname: Rahbari
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Renxin
authors.initials: R
authors.lastname: Chu
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Keren
authors.initials: K
authors.lastname: Regev
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Pia
authors.initials: P
authors.lastname: Kivisäkk
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Partners Multiple Sclerosis Center (R.B., S. Tauhid, S. Tummala, R.C., H.L.W.) and Ann Romney Center for Neurologic Diseases (R.B., A.Y., B.P., R.R., K.R., P.K., H.L.W., F.J.Q.), Neurology (R.B., A.Y., B.P., S. Tauhid, S. Tummala, R.R., R.C., K.R., P.K., H.L.W., F.J.Q.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana