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AB0033 Intracellular Expression of Survivin and Bcl-6 is Decreased in CD4+ T-Cells of Rheumatoid Arthritis Patients with High Serum Survivin
  1. M. Turkkila,
  2. N. Filluelo Cavallini,
  3. S. Töyrä Silfverswärd,
  4. M. Erlandsson,
  5. M. Brisslert,
  6. R. Pullerits,
  7. K. Andersson,
  8. M. Bokarewa
  1. University of Gothenburg, Gothenburg, Sweden

Abstract

Background Survivin is recognized as a marker of persistently active and erosive RA. The findings in experimental arthritis suggested that survivin co-ordinates the antigen-dependent leukocyte maturation and function by regulating transcriptional activity of Bcl-6, essential factor of germinal center formation and a factor involved neoplastic transformation to lymphoma.

Objectives We studied intracellular expression of survivin and Bcl-6 in the peripheral lymphocytes and its relation to clinical features and treatment of RA patients.

Methods The intracellular expression of survivin and Bcl-6 was studied on the effector and memory subsets of CD4+ and CD8+ T-cells and in CD19+ B-cells in 18 RA patients using flow cytometry. Serum and mRNA levels of survivin were analysed in 144 RA patients (age 21-71 years, disease duration 1-49 years) using ELISA and qPCR, respectively. Patients with serum levels of survivin >0.45 ng/mL comprised the serum survivin-positive (sSurv+) group.

Results The sSurv+ group (n=76) was characterized by higher frequency of RF+ and aCCP+ patients, as well as by higher levels of aCCP and of differentiation factor Flt3-ligand compared to sSurv (n=68). The sSurv+ and sSurv- patients were similar with respect to age, disease duration, DAS28 and anti-rheumatic treatment. Intracellular mRNA levels of Bcl-6 were lower in sSurv+ compared to sSurv patients, while RNA of survivin were similar. Flow cytometry showed that survivin was present in >85% of non-stimulated T-cells and B-cells lymphocytes of RA patients. The survivinhi subset comprised 2-14% of T-cells and was enriched in the effector (CD62Lneg) population of CD4+ T-cells compared to central memory and naïve CD4+ T-cells. The expression of Bcl-6 was found within 7-38% of survivin+ effector CD4+ T-cells and in 21-69% of CD19+ B-cells. The subsets of survivin+ and of survivin+Bcl-6+ T-cells was smaller in the sSurv+ patients compared to sSurv patients, and was inversely correlated to the levels of serum survivin in these patients. The subset of survivin+Bcl-6+ B-cells was similar in sSurv+ and sSurv- patients.

Conclusions In this pilot study we demonstrate that RA patients have co-expression of the two oncoproteins involved in neoplastic transformation to lymphoma, survivin and Bcl-6.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5490

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