title: Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients.
abstract: BACKGROUND
  Autoreactive antibodies (ARAB) occur more frequently in patients with multiple sclerosis (MS) than in general population and the presence of these antibodies often causes uncertainty regarding the disease course, response to therapy and the diagnosis of MS.
  
  
  METHODS
  Retrospective analyses of the ARAB, clinical and MRI data of a consecutive patient cohort of MS and clinically isolated syndrome (CIS) patients were conducted. The patients were evaluated for an extensive panel that included various subtypes of antiphospholipid antibody (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti-SS-B antibodies. Quantitative MRI analysis was performed in a subgroup of MS patients measuring T2-lesion volume (LV), T1 black hole LV and brain parenchymal fraction (BPF).
  
  
  RESULTS
  A total of 137 patients (mean age 44.7, 84% female) with either MS (n=111; age: mean 46.5+/-S.D. 10.3 years; disease duration: mean 13.0+/-S.D. 10.4 years; EDSS: mean 3.2+/-S.D. 1.9) or CIS (n=26; age: mean 37.7+/-S.D. 7.8 years; disease duration: mean 1.3+/-S.D. 1.1 years; EDSS: mean 1.0+/-S.D. 0.7) were enrolled. Among MS patients, 82 were RRMS, 26 SPMS, and 3 had PPMS. Seventy-seven (69%) of MS patients showed presence of one or more ARAB. The proportion of MS patients with APLA was 55% (61 patients); IgM subtype was most frequent. Co-occurrence of ACA and APE was more frequent in SPMS as compared to RRMS (15.4% vs. 1.2%, p=0.012). The proportion of CIS patients with ARAB was 75% with IgM subtype being the most frequent. However, the ARAB in majority of CIS patients (9 out of 14, 64%) were transient on repeated testing. In a subgroup of 62 MS patients, quantitative MRI analysis showed significantly higher T2-LV in patients with positive APLA (15.1 ml for APLA positive vs. 6.75 ml for APLA negative) after correcting for the disease duration (p=0.048). The patients with ATA also had significantly higher T2-LV after correction for disease duration (19.0 ml vs.8.5, p=0.044).
  
  
  CONCLUSIONS
  ARAB were present in more than two thirds of MS and CIS patients although most of APLA in CIS were transient. The presence of APLA in MS patients was associated with higher T2-LV.
authors.affiliation: Multiple Sclerosis Center, UMass Memorial Medical Center, Worcester, MA 01605, USA. neetagarg@hotmail.com
authors.forename: Neeta
authors.initials: N
authors.lastname: Garg
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Irene
authors.initials: I
authors.lastname: Vasiliu
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Locke
authors.forename: Kelly
authors.initials: K
authors.lastname: Watts
authors.forename: Jordan
authors.initials: J
authors.lastname: Lema
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Rajeswary
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Munschauer
authors.forename: Julian
authors.initials: J
authors.lastname: Ambrus
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*; D010743:Phospholipids / Q000145:classification / Q000276:immunology*; D012189:Retrospective Studies; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D001323:Autoantibodies; D010743:Phospholipids