title: Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.
abstract: OBJECTIVE
  To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS).
  
  
  METHODS
  Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies.
  
  
  RESULTS
  Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008).
  
  
  CONCLUSIONS
  High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS.
authors.affiliation: Department of Neurology and Neurosurgery, University Hospital of Pleven, Georgi Kochev st 8A, Pleven 5800, Bulgaria. Electronic address: tzvetanovplamen@hotmail.com.
authors.forename: Behidhe
authors.initials: B
authors.lastname: Sadarzanska-Terzieva
authors.affiliation: Department of Clinical Neurophysiology, Sandringham level 1, Leicester Royal Infirmary, University Hospital of Leicester, Leicester LE1 5WW, UK.
authors.forename: Plamen
authors.initials: P
authors.lastname: Tzvetanov
authors.affiliation: Department of Neurosciences, University Hospital of Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK.
authors.forename: Vishwajit
authors.initials: V
authors.lastname: Hegde
authors.affiliation: Department of Neurology, Ibn-Sina Hospital, Kuwait, POB 25427, Safat 13115, Kuwait.
authors.forename: Jasem Y
authors.initials: JY
authors.lastname: Al-Hashel
authors.affiliation: Department of Neurology, Ibn-Sina Hospital, Kuwait, POB 25427, Safat 13115, Kuwait.
authors.forename: Rossen Т
authors.initials: RТ
authors.lastname: Rousseff
authors.affiliation: National Hospital in Cardiology, Neurology Clinic, 65 Konjovitsa Str., Sofia 1309, Bulgaria.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Haralanov
authors.affiliation: Department of Neurology and Neurosurgery, University Hospital of Pleven, Georgi Kochev st 8A, Pleven 5800, Bulgaria.
authors.forename: Boyko
authors.initials: B
authors.lastname: Stamenov
authors.affiliation: Department of Biology, Medical University of Pleven, Kliment Ohridski St. 1, Pleven 5800, Bulgaria.
authors.forename: Milena
authors.initials: M
authors.lastname: Atanassova
authors.affiliation: Department of Psychology, Affiliate "Prof Ivan Mitev" of Vratza, Medical University of Sofia, School Complex 1, Vratza 3000, Bulgaria.
authors.forename: Iveta
authors.initials: I
authors.lastname: Marinova
authors.affiliation: Department of Psychology, Affiliate "Prof Ivan Mitev" of Vratza, Medical University of Sofia, School Complex 1, Vratza 3000, Bulgaria.
authors.forename: Anna
authors.initials: A
authors.lastname: Marinova
authors.affiliation: Department of Clinical Laboratory, University Hospital of Pleven, Georgi Kochev St. 8A, Pleven 5800, Bulgaria.
authors.forename: Adelaida
authors.initials: A
authors.lastname: Rousseva
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D024141:Collagen Type IV / Q000276:immunology*; D003711:Demyelinating Diseases / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis; D010865:Pilot Projects; D011379:Prognosis; D012306:Risk; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D024141:Collagen Type IV; C048844:anti-IgG; C044203:anti-IgM; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1
keywords: Anti-collagen type IV antibodies; Clinically isolated syndrome; Matrix metalloproteinases; Metalloproteinases inhibitor; Multiple sclerosis