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SAT0109 Immortal fibroblast-like synoviocytes in rheumatoid arthritis & disease severity: How far is the antiapoptotic protein BCL-2 expression involved?
  1. N. Abaza1,
  2. F. Abdel-Motaal1,
  3. M. Mansour1,
  4. N. Shaker1,
  5. N. Elhefnawi2,
  6. B. Bedeir3,
  7. S. Mansi4
  1. 1Rheumatology and Rehabilitation
  2. 2Pathology, Faculty of Medicine, Ainshams University, Cairo
  3. 3Pathology, Faculty of Medicine Alazhar University
  4. 4Pathology, Theodor Bilhar, Cairo, Egypt

Abstract

Background Immortality, aggressiveness and tumor-like behavior of fibroblasts-like synoviocytes (FLS) are to be blamed for the joint damage in rheumatoid arthritis (RA). The lack of apoptosis is a hallmark of these FLS in RA synovium and the molecular basis responsible for such a lack involves many antiapoptotic proteins including the bcl-2 family. Named after it, this family pronounces the importance of this particular protein being crucial and pivotal in apoptosis.

Objectives To estimate bcl-2 expression in RA synovium - specially FLS – in relation to disease severity, synovial hyperplasia & aggressiveness, high-lightening future therapeutic interventions.

Methods Synovium from 10 RA patients, 10 Osteoarthritis (OA) patients & 6 healthy post-traumatic control were studied for histological (number of cell layers, cell types & arrangement) and ultrastructural assessment (apoptotic features and tumor-like behavior features: prominent nucleolus, dispersed chromatin and rich dilated endoplasmic reticulum with wide cysternae) using light & electron microscopy respectively. Severity of RA was assessed using Steinbrocker classification of progression of RA. Immunohistochemistry staining of bcl-2 was performed measuring its expression percent by cell analysis system (CAS 200) image analyser and correlation with disease severity.

Results Area percentage of bcl-2 expression in FLS was significantly higher in RA group (17.54±12.19%) in comparison to OA (4±6.43%) and heathy post-traumatic control (0.83±1.59%) groups (p<0.01) and in lymphocytes in RA group compared to both groups (p<0.001). No statistical significant difference was detected between OA and post-traumatic groups. Our results also demonstrated a highly significant positive correlation between bcl-2 positive FLS and bcl-2 positive lymphocytes in RA (r=0.89, p<0.01) as well as between each and disease severity (r=0.88, p<0.01 and r=0.83, p<0.01 respectively) and number of cell layer in synovial hyperplasia (r=0.89, p<0.01 and r=0.97, p<0.01 respectively). Estimated percentage of FLS showing apoptotic features in RA was the lowest (19.8%) compared to the other groups. RA FLS showed tumor-like ultrastructural features.

Conclusions Bcl-2 overexpression in RA synovium leads to a generation of death-resistant aggressive FLS and immortal effector cells, hence playing a pivotal role in pathogenesis and severity of RA. Potential damage control and better disease prognosis can be obtained by targeting such anti-apoptotic protein. Controlling bcl-2 expression level would be of great benefit to decelerate, minimize or prevent joint damage in RA.

  1. Perlman et al., Journal of immunology 2000; 164:5227-35.

  2. Matsumoto et al., Journal of Rheumatology 1996; 23(8):1345-52.

Disclosure of Interest None Declared

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