Serum protein signatures detect early radiographic osteoarthritis.
OBJECTIVE
To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident.


METHODS
Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case-control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques.


RESULTS
Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA.


CONCLUSIONS
Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years.
National Institute on Aging Intramural Research Program, National Institutes of Health (NIH), Baltimore, MD 21225, United States. lingsh@grc.nia.nih.gov
S M
SM
Ling
D D
DD
Patel
P
P
Garnero
M
M
Zhan
M
M
Vaduganathan
D
D
Muller
D
D
Taub
J M
JM
Bathon
M
M
Hochberg
D R
DR
Abernethy
E J
EJ
Metter
L
L
Ferrucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000175:diagnosis* / Q000000981:diagnostic imaging; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000000981:diagnostic imaging; D040081:Protein Array Analysis / Q000379:methods; D011859:Radiography; D055815:Young Adult
D015415:Biomarkers; D001798:Blood Proteins