title: Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes before and after disease onset.
abstract: METHODS
  We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in individuals at risk for or with type 1 diabetes including: (i) 58 established type 1 and 2 diabetic patients; (ii) 34 autoantibody positive (AA+) children and adults; (iii) 164 infants and young children with insulin-dependent diabetes mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; and (iv) 37 healthy control individuals, over a 5-yr period.
  
  
  RESULTS
  Established type 1 diabetic patients (1 month to 30+ yr post-disease onset) had significantly higher PGS2 expression than healthy controls; by contrast, insulin-treated type 2 diabetic patients had significantly lower PGS2 expression than healthy controls. Longitudinal studies of AA+ subjects at risk for type 1 diabetes indicated that 73% (11/15) of individuals who developed this disease during the study period expressed high levels of PGS2 prior to or after onset. We also found high level PGS2 expression in genetically at-risk infants and young children that correlated with having a first-degree relative with type 1 diabetes, but not with age, gender, or HLA genotype. In this population, high level PGS2 expression coincided with or preceded autoantibody detection in 30% (3/10) of subjects.
  
  
  CONCLUSIONS
  These findings suggest that high level monocyte PGS2 expression, although subject to fluctuation, is present in at-risk subjects at an early age and is maintained during progression to and after type 1 diabetes onset.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Box 100275, JHMHC, Gainesville, Florida 32610, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Litherland
authors.forename: J X
authors.initials: JX
authors.lastname: She
authors.forename: D
authors.initials: D
authors.lastname: Schatz
authors.forename: K
authors.initials: K
authors.lastname: Fuller
authors.forename: A D
authors.initials: AD
authors.lastname: Hutson
authors.forename: R H
authors.initials: RH
authors.lastname: Peng
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: K M
authors.initials: KM
authors.lastname: Grebe
authors.forename: D S
authors.initials: DS
authors.lastname: Whittaker
authors.forename: K
authors.initials: K
authors.lastname: Bahjat
authors.forename: D
authors.initials: D
authors.lastname: Hopkins
authors.forename: Q
authors.initials: Q
authors.lastname: Fang
authors.forename: P D
authors.initials: PD
authors.lastname: Spies
authors.forename: K
authors.initials: K
authors.lastname: North
authors.forename: C
authors.initials: C
authors.lastname: Wasserfall
authors.forename: R
authors.initials: R
authors.lastname: Cook
authors.forename: M A
authors.initials: MA
authors.lastname: Dennis
authors.forename: S
authors.initials: S
authors.lastname: Crockett
authors.forename: J
authors.initials: J
authors.lastname: Sleasman
authors.forename: J
authors.initials: J
authors.lastname: Kocher
authors.forename: A
authors.initials: A
authors.lastname: Muir
authors.forename: J
authors.initials: J
authors.lastname: Silverstein
authors.forename: M
authors.initials: M
authors.lastname: Atkinson
authors.forename: M J
authors.initials: MJ
authors.lastname: Clare-Salzler
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002675:Child, Preschool; D051546:Cyclooxygenase 2; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000097:blood*; D008297:Male; D008565:Membrane Proteins; D009000:Monocytes / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases