title: The expression of VEGF-A is down regulated in peripheral blood mononuclear cells of patients with secondary progressive multiple sclerosis.
abstract: BACKGROUND
  Most patients with relapsing-remitting multiple sclerosis (RRMS) eventually enter a secondary progressive (SPMS) phase, characterized by increasing neurological disability. The mechanisms underlying transition to SPMS are unknown and effective treatments and biomarkers are lacking. Vascular endothelial growth factor-A (VEGF-A) is an angiogenic factor with neuroprotective effects that has been associated with neurodegenerative diseases. SPMS has a prominent neurodegenerative facet and we investigated a possible role for VEGF-A during transition from RRMS to SPMS.
  
  
  RESULTS
  VEGF-A mRNA expression in peripheral blood mononuclear (PBMC) and cerebrospinal fluid (CSF) cells from RRMS (n = 128), SPMS (n = 55) and controls (n = 116) were analyzed using real time PCR. We demonstrate reduced expression of VEGF-A mRNA in MS CSF cells compared to controls (p<0.001) irrespective of disease course and expression levels are restored by natalizumab treatment(p<0.001). VEGF-A was primarily expressed in monocytes and our CSF findings in part may be explained by effects on relative monocyte proportions. However, VEGF-A mRNA expression was also down regulated in the peripheral compartment of SPMS (p<0.001), despite unchanged monocyte counts, demonstrating a particular phenotype differentiating SPMS from RRMS and controls. A possible association of allelic variability in the VEGF-A gene to risk of MS was also studied by genotyping for six single nucleotide polymorphisms (SNPs) in MS (n = 1114) and controls (n = 1234), which, however, did not demonstrate any significant association between VEGF-A alleles and risk of MS.
  
  
  CONCLUSIONS
  Expression of VEGF-A in CSF cells is reduced in MS patients compared to controls irrespective of disease course. In addition, SPMS patients display reduced VEGF-A mRNA expression in PBMC, which distinguish them from RRMS and controls. This indicates a possible role for VEGF-A in the mechanisms regulating transition to SPMS. Decreased levels of PBMC VEGF-A mRNA expression should be further evaluated as a biomarker for SPMS.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institute Solna, Center for Molecular Medicine, Stockholm, Sweden. Ellen.Iacobaeus@karolinska.se
authors.forename: Ellen
authors.initials: E
authors.lastname: Iacobaeus
authors.forename: Petra
authors.initials: P
authors.lastname: Amoudruz
authors.forename: Mikael
authors.initials: M
authors.lastname: Ström
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Lou
authors.initials: L
authors.lastname: Brundin
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Emma
authors.initials: E
authors.lastname: Tham
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A