title: Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjogren's syndrome patients.
abstract: OBJECTIVE
  To determine the expression and enzymatic activities of sulphotransferases involved in mucin hyposulphation in labial salivary glands (LSGs) from SS patients and to correlate sulphotransferase activity with clinical parameters such as secretion, inflammation and serology.
  
  
  METHODS
  LSG from 31 SS patients and 31 control subjects were studied. Relative mRNA and protein levels of Gal3-O-sulphotransferases (Gal3STs) and β1,3-galactosyltransferase-5 (β3GalT5) were determined by quantitative RT-PCR and western blotting, respectively. Enzymatic activities were quantified using radioactively labelled donor substrates and specific acceptor substrates. Products were purified by chromatography. Spearman's correlation analysis was used to compare data.
  
  
  RESULTS
  The levels of Gal3ST activity were significantly decreased in SS patients, without changes in mRNA and protein levels, while the enzymatic activities of glycosyltransferases involved in mucin glycosylation were similar in both groups. An inverse correlation was observed between Gal3ST activity and glandular function measured by scintigraphy, but not with unstimulated salivary flow. Gal3ST activity was inversely correlated with focus score, TNF-α levels and presence of the autoantibodies Ro/SS-A and La/SS-B.
  
  
  CONCLUSIONS
  The decrease in sulphotransferase activity provides an explanation for mucin hyposulphation observed in the LSGs from SS patients. The decrease in Gal3STs activity was not a consequence of reduced gene expression, but probably due to alterations in the enzyme activity regulation. Interestingly, the levels of sulphotransferase activity detected correlated well with secretory function, inflammation and serology. Finally, we postulate that pro-inflammatory cytokines induced by autoantibodies, such as Ro/SS-A and La/SS-B in SS patients, may modulate Gal3ST activity, thereby altering mucin quality and leading to mouth dryness.
authors.affiliation: Institute of Biomedical Sciences, University of Chile, Casilla, Chile.
authors.forename: Isabel
authors.initials: I
authors.lastname: Castro
authors.forename: Sergio
authors.initials: S
authors.lastname: Aguilera
authors.forename: Inka
authors.initials: I
authors.lastname: Brockhausen
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alliende
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: Claudio
authors.initials: C
authors.lastname: Molina
authors.forename: Ulises
authors.initials: U
authors.lastname: Urzúa
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.forename: Verónica
authors.initials: V
authors.lastname: Bahamondes
authors.forename: María-José
authors.initials: MJ
authors.lastname: Barrera
authors.forename: Marianela
authors.initials: M
authors.lastname: Sánchez
authors.forename: Sergio
authors.initials: S
authors.lastname: González
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermoso
authors.forename: Cecilia
authors.initials: C
authors.lastname: Leyton
authors.forename: María-Julieta
authors.initials: MJ
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D015551:Autoimmunity; D015153:Blotting, Western; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005700:Galactosyltransferases / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012470:Salivary Glands, Minor / Q000201:enzymology*; D012859:Sjogren's Syndrome / Q000201:enzymology*; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D055257:Mucin-5B; D012333:RNA, Messenger; C479886:B3GALT5 protein, human; D005700:Galactosyltransferases; D013466:Sulfurtransferases; C432419:GAL3ST2 protein, human; D015238:Sulfotransferases