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.
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Matsumoto et al., Journal of Rheumatology 1996; 23(8):1345-52.
Disclosure of Interest None Declared
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