Role of apo-IFas and caspase-3 in the pathogenesis & manifestations of rheumatoid arthritis

Abstract EN

Hypothesis: In most tissues, cell division occurs continuously, without an increase in organ size or tumor development.

This suggests that the rate of cell division is balanced by programmed cell death.

This balance by programmed cell death, or apoptosis, follows a stereotypical pattern of morphological changes, irrespective of the initiating event.

A breakdown in the delicate balance between cell survival and apoptosis has been implicated in the pathogenesis of a number of rheumatic diseases including rheumatoid arthritis (RA).

Methodology: Apo-I/Fas the apoptotic inducer together with the executioner caspase-3 were determined in 32 RA patients as well as 16 matching healthy controls.

Results: The study revealed significantly increased Apo-1/Fas and caspase-3 in RA patients as compared to controls.

Patients treated with NSAIDs showed an insignificantly higher Apo-1/Fas and caspase-3 as compared to patients on steroids.

In a similar manner, patients with advanced x-ray grading showed insignificantly lower Apo-1/Fas and caspase-3 as compared to patients with early lesions.

The levels of Apo-1/Fas and caspase-3 correlated significantly in a negative manner with hemoglobin levels.

It is also positively correlated with ESR2, which is one of 2 indices of RA activity.

Also, Apo-1/Fas and caspase-3 correlated positively with each other.

Conclusion: The present findings would suggest that disturbed apoptosis is present in RA, a disease characterized by synovial proliferation with infiltration of inflammatory cells.

There are two distinct pathways in the pathogenesis of RA: T-cell-mediated immune response and proliferation of synovial cells.

However, the process involving proliferation of synovial cells regresses and is gradually replaced with fibrous tissue formation.

The majority of activated T-cells infiltrating the synovium express functional Fas antigen and Fas ligand.

Thus, Fas mediated apoptosis via at least in part, caspase-3 activation could be involved in RA pathogenesis.

Tetrapeptide inhibitors can selectively block different caspases and arrest programmed cell death.

Alternatively, intraarticular administration of anti-Fas antibody to animal models of RA produced marked improvement.

These new interventions could prove to be successful therapeutic modalities in near future.