title: Specific glycosylation of alpha(1)-acid glycoprotein characterises patients with familial Mediterranean fever and obligatory carriers of MEFV.
abstract: BACKGROUND
  Familial Mediterranean fever (FMF) is a periodic febrile disorder, characterised by fever and serositis. The acute phase response during attacks of FMF results from the release of cytokines, which in turn induce increased expression and changed glycosylation of acute phase proteins. A recent study indicated that attacks in FMF are accompanied by a rise of plasma concentrations of serum amyloid A (SAA) and C reactive protein (CRP), which remain significantly raised during remission relative to healthy controls. Another study suggested that obligatory heterozygotes also display an inflammatory acute phase response.
  
  
  OBJECTIVE
  To determine the state of inflammation in homozygotic and heterozygotic MEFV genotypes.
  
  
  METHODS
  CRP and SAA were studied by enzyme linked immunosorbent assay (ELISA). The glycosylation of the acute phase protein, alpha(1)-acid glycoprotein (AGP), was visualised with crossed affinoimmunoelectrophoresis with concanavalin A as diantennary glycan-specific component and Aleuria aurantia lectin as fucose-specific affinity component.
  
  
  RESULTS
  FMF attacks were associated with an increase (p<0.05) in the serum inflammation parameters CRP, SAA, and AGP. The glycosylation of AGP showed an increase (p<0.05) in fucosylated AGP glycoforms, whereas the branching of the glycans remained unaffected. The glycosylation of AGP in the MEFV carrier group, compared with that in a healthy control group, was characterised by a significant increase (p<0.05) in branching of the glycans, whereas the fucosylation remained unaffected.
  
  
  CONCLUSIONS
  The findings suggest an FMF-specific release of cytokines, resulting in a different glycosylation of AGP between a homozygotic and heterozygotic MEFV genotype.
authors.affiliation: Department of Medical Chemistry, Institute for Inflammation and Inflammatory Diseases, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Poland
authors.forename: J P
authors.initials: JP
authors.lastname: Drenth
authors.forename: E
authors.initials: E
authors.lastname: Rabinovitz
authors.forename: A
authors.initials: A
authors.lastname: Livneh
authors.forename: J
authors.initials: J
authors.lastname: Bijzet
authors.forename: B
authors.initials: B
authors.lastname: van het Hof
authors.forename: W
authors.initials: W
authors.lastname: van Dijk
mesh_terms: D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D010505:Familial Mediterranean Fever / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D009961:Orosomucoid / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin; D000685:Serum Amyloid A Protein / Q000032:analysis; D018709:Statistics, Nonparametric
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D009961:Orosomucoid; D011506:Proteins; D000071198:Pyrin; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein