Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis: a pilot studyReport as inadecuate

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Arthritis Research and Therapy

, 16:R45

First Online: 05 February 2014Received: 06 March 2013Accepted: 28 January 2014


IntroductionAntibodies against citrullinated peptides anti-CCP and increased levels of cytokines precede the development of rheumatoid arthritis RA by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand Flt3L have been identified as biomarkers of RA associated with joint destruction. Our objective was to investigate the potential of survivin and Flt3L as predictors of RA in samples from patients prior to onset of symptoms.

MethodsThis study included 47 individuals sampled before onset of RA median 2.5 years IQR 4.5 and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using ELISAs and 29 cytokines-chemokines by multiplex detection.

ResultsLevels of survivin were increased in pre-symptomatic individuals compared with controls P = 0.003, whilst the levels of Flt3L were similar. The frequency of survivin positivity in the pre-symptomatic individuals was increased compared with the controls 36.2 vs.14.2%, P = 0.001 and predicted disease development odds ratio OR =3.4 95% confidence interval CI 1.6-7.2. The frequency of survivin and Flt3L in RA patients was increased compared with the controls both, P <0.0001, OR = 12.1 95% CI, 5.3-27.6 and OR = 11.0 95% CI, 3.9-30.9, respectively. Anti-CCP positive pre-symptomatic individuals and patients had significantly higher levels of survivin compared with anti-CCP2 negative individuals. In pre-symptomatic individuals, survivin correlated with IL-12, IL-1β and IL-9 whereas Flt3L correlated to a significantly broader spectrum of cytokines in RA patients.

ConclusionProto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting its role at pre-clinical stages of the disease.

Abbreviationsanti-CCPanti-cyclic citrullinated peptide antibodies

ELISAenzyme-linked immunosorbent assay

Flt3LFms-like tyrosine kinase 3 ligand


RArheumatoid arthritis

ThT-helper type.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4474 contains supplementary material, which is available to authorized users.

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Author: Maria Bokarewa - Mikael Brink - Malin Erlandsson - Solbritt Rantapää Dahlqvist


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