Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes before and after disease onset.
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.
Litherland
S A
SA
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Box 100275, JHMHC, Gainesville, Florida 32610, USA.
She
J X
JX
Schatz
D
D
Fuller
K
K
Hutson
A D
AD
Peng
R H
RH
Li
Y
Y
Grebe
K M
KM
Whittaker
D S
DS
Bahjat
K
K
Hopkins
D
D
Fang
Q
Q
Spies
P D
PD
North
K
K
Wasserfall
C
C
Cook
R
R
Dennis
M A
MA
Crockett
S
S
Sleasman
J
J
Kocher
J
J
Muir
A
A
Silverstein
J
J
Atkinson
M
M
Clare-Salzler
M J
MJ
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*
D001323:Autoantibodies; D006680:HLA Antigens; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases