Abstract
IntroductionHigh levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The aim of this study was to investigate the reproducibility of survivin status and its significance for clinical and immunological assessment of RA patients.MethodsSurvivin levels were measured in 339 patients from the Better Anti-Rheumatic FarmacOTherapy (BARFOT) cohort of early RA at baseline and after 24 months. The association of survivin status with joint damage (total Sharp-van der Heijde score), disease activity (Disease Activity Score based on evaluation of 28 joints (DAS28)), functional disability (Health Assessment Questionnaire (HAQ)), and pain perception (Visual Analogue Scale (VAS)) was calculated in the groups positive and negative for survivin on both occasions, and for the positive-negative and negative-positive groups.ResultsIn 268 patients (79%) the levels of survivin were similar at baseline and after 24 months, 15% converted from survivin-positive to survivin-negative, and 5% from survivin-negative to survivin-positive. A combination of smoking and antibodies against cyclic citrullinated peptides (aCCP) predicted persistently (baseline and 24 months) high levels of survivin (odds ratio 4.36 (95% CI: 2.64 to 7.20), P < 0.001), positive predictive value 0.66 and specificity 0.83). The independent nature of survivin and aCCP was demonstrated by statistical and laboratory analysis. Survivin positivity on both test occasions was associated with the progression of joint damage, significantly higher DAS28 and lower rate of remission at 24 and 60 months compared to negative-negative patients. Survivin status was less associated with changes in HAQ and VAS.ConclusionsSurvivin is a relevant and reproducible marker of severe RA. Persistently high levels of survivin were associated with smoking and the presence of aCCP and/or RF antibodies and predicted persistent disease activity and joint damage.
Highlights
High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA)
A combination of smoking and antibodies against cyclic citrullinated peptides predicted persistently high levels of survivin (odds ratio 4.36, P < 0.001), positive predictive value 0.66 and specificity 0.83)
The independent nature of survivin and antibodies against cyclic citrullinated peptide (aCCP) was demonstrated by statistical and laboratory analysis. Survivin positivity on both test occasions was associated with the progression of joint damage, significantly higher DAS28 and lower rate of remission at 24 and 60 months compared to negative-negative patients
Summary
High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). The course of rheumatoid arthritis (RA) may vary considerably, from early and long-lasting remission to persistent disabling joint damage [1,2]. Reliable predictors of the aggressive and therapy-resistant RA [6,7,8,9] Their predictive ability in individual patients is hampered by limited specificity. We have recently found that RA patients with high levels of oncoprotein survivin in serum and synovial fluid have persistent joint inflammation and damage [10]. The results obtained in an independent cohort of RA patients showed that survivin was associated with a therapy-resistant course of arthritis, poor response to biological treatment [16] and a low remission rate [11]. Survivin is frequently found in conjunction with aCCPs and RF, and the combination of survivin with these autoantibodies enhances the predictive power of survivin
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