Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis

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Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis. / Svensson, Björn; Hafström, Ingiäld; Forslind, Kristina; Albertsson, Kristina; Tarkowski, Andrej; Bokarewa, Maria.

In: Annals of Medicine, Vol. 42, No. 1, 01.02.2010, p. 45-54.

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Svensson, Björn ; Hafström, Ingiäld ; Forslind, Kristina ; Albertsson, Kristina ; Tarkowski, Andrej ; Bokarewa, Maria. / Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis. In: Annals of Medicine. 2010 ; Vol. 42, No. 1. pp. 45-54.

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TY - JOUR

T1 - Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis

AU - Svensson, Björn

AU - Hafström, Ingiäld

AU - Forslind, Kristina

AU - Albertsson, Kristina

AU - Tarkowski, Andrej

AU - Bokarewa, Maria

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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. Patients and 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 Mkinen. 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. Conclusion. Detection of survivin in early RA predicted joint destruction and failure of achieving remission after 5 years in patients with early RA.

AB - 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. Patients and 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 Mkinen. 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. Conclusion. Detection of survivin in early RA predicted joint destruction and failure of achieving remission after 5 years in patients with early RA.

KW - Oncogenes

KW - Prognosis

KW - Remission

KW - Rheumatoid arthritis

KW - Survivin

UR - http://www.scopus.com/inward/record.url?scp=75149157986&partnerID=8YFLogxK

U2 - 10.3109/07853890903376280

DO - 10.3109/07853890903376280

M3 - Article

VL - 42

SP - 45

EP - 54

JO - Annals of Clinical Research

T2 - Annals of Clinical Research

JF - Annals of Clinical Research

SN - 1365-2060

IS - 1

ER -