Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis.
BACKGROUND
Rheumatoid arthritis (RA) is characterized by an uncontrolled spread of destructive joint inflammation resembling malignancy. Epidemiological studies have established strong correlation between inflammation and predisposition for cancer. Here we assess the predictive role of the circulating proto-oncogene survivin for clinical and radiological outcome of early RA.


METHODS
Serum survivin was measured by sandwich ELISA in 651 patients with early RA (mean duration 6 months). X-rays of hands and feet were prospectively obtained at base-line and after 1, 2, and 5 years and evaluated for the presence of bone destruction by a modified Sharp method. The predictive value of survivin for radiological destruction was calculated using multivariate regression models including antibodies against cyclic citrullinated peptides (aCCP) and rheumatoid factor (RF). Remission was assessed by the EULAR (European League Against Rheumatism) criteria and by criteria proposed by Mäkinen.


RESULTS
At base-line, 391 patients (60%) had high levels of survivin. Radiological progression at 5 years was significantly more frequent (P= 0.001) among survivin-positive patients than among survivin-negative. Survivin positivity predicted radiological progression independently of aCCP and RF. The positive predictive value of survivin was proved both in the group of patients with and in the group without erosions at base-line. The combination of positive tests for both survivin and aCCP had the highest prediction for radiological progression (positive predictive value 0.75). Additionally, a positive test for survivin was an independent predictor of not being in remission.


CONCLUSIONS
Detection of survivin in early RA predicted joint destruction and failure of achieving remission after 5 years in patients with early RA.
Svensson
Björn
B
Section of Rheumatology at the Institution of Clinical Science, University Hospital, Lund, Sweden.
Hafström
Ingiäld
I
Forslind
Kristina
K
Albertsson
Kristina
K
Tarkowski
Andrej
A
Bokarewa
Maria
M
D000328:Adult; D000368:Aged; D000906:Antibodies; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000097:blood*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood; D011446:Prospective Studies; D000090063:Proto-Oncogene Mas; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood; D012460:Sulfasalazine / Q000627:therapeutic use; D000077022:Survivin; D016896:Treatment Outcome
D000906:Antibodies; D018501:Antirheumatic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C000715470:MAS1 protein, human; D008869:Microtubule-Associated Proteins; D010456:Peptides, Cyclic; D000090063:Proto-Oncogene Mas; D000077022:Survivin; C487763:cyclic citrullinated peptide; D012460:Sulfasalazine; D012217:Rheumatoid Factor; D008727:Methotrexate