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Apoptosis or programmed cell death is one of the regulation mechanisms of cell homeostasis.
Fas is a transmembrane receptor protein which transmits a cell death signal when cross linked with an antibody or with its physiological ligand—Fas ligand (Fas L).1 Fas and Fas L have a pivotal role in regulating lymphocyte apoptosis and maintaining lymphocyte homeostasis.
Soluble forms of Fas and Fas L may be detectable and measured in the serum,2 and may reflect the activation of this pathway. Moreover, soluble forms of Fas regulate Fas/Fas L mediated apoptosis.3 Raised levels of soluble Fas (sFas) have been shown in various chronic inflammatory rheumatic diseases, systemic lupus erythematosus, Sjögren's syndrome,1 4 5 and in the synovial fluid of rheumatoid arthritis.6 These diseases are autoimmune diseases with lymphocyte involvement.
Ankylosing spondylitis (AS) is another chronic inflammatory rheumatic disorder, with less autoimmune background or lymphocyte involvement. Involvement of apoptosis in the pathogenesis of AS has not been discounted.
This preliminary study aimed at evaluating the apoptotic Fas/Fas L system in AS by measuring the amount of the soluble forms of these proteins in the serum of patients with AS compared with controls.
Forty nine consecutive inpatients and outpatients with AS according to the revised New York criteria were included.7Forty healthy subjects without any inflammatory or autoimmune disease, with the same age and sex distribution, were used as controls.
For the patients with AS the disease activity was assessed by clinical variables (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI))8 and biological variables (erythrocyte sedimentation rate (ESR), serum C reactive protein (CRP) levels).
Soluble Fas (sFas) and soluble Fas Ligand (sFas L) levels were measured twice in the serum of the patients and controls using a sandwich enzyme linked immunosorbent assay (ELISA) (sFas ELISA kit and sFas L ELISA kit; Medical and Biological Laboratoires Co, Ltd, Nagoya Japan). Statistical analysis was by Student's ttest.
Of the 49 patients (34 men, 15 women), with a mean (SD) disease duration of 8.6 (7.2) years, 40 (82%) were HLA-B27 positive. The mean BASDAI index was 5.34 (1.97), mean ESR 24.9 (22.7) mm/1st h, and mean CRP 16.0 (18.8) mg/l.
There were no differences in the serum levels of sFas and sFas L between patients with AS and controls (table 1).
Moreover, no differences were found in the sFas and sFas L serum levels between patients with active and inactive AS (table 2). For 26 patients the BASDAI was >5.3 and for 23 patients <5.2. Similarly, 19 patients had an ESR >25 mm/1st h and in 30 patients the ESR was <25 mm/1st h. CRP was >16 mg/l in 17 patients and < 16 mg/l in 32. The split between the groups was defined by the mean of the values.
This study failed to show any modification in serum levels of sFas and sFas L in patients with AS compared with controls. There were no differences between patients with clinically or biologically active and inactive AS, and so there was no correlation with disease activity.
These results are in contrast with the results found with other chronic inflammatory autoimmune rheumatic diseases.1 4 5However, Fas levels do not seem to correlate with the clinical diagnosis of autoimmune disease, or laboratory abnormalities.9 AS differs from these conditions as there is no lymphocyte activation,10 but involvement of polymorphonuclear cells and intracellular chronic infection. These mechanisms do not seem to interfere with apoptosis. For example, it has been shown that clearance of Chlamydia trachomatis(a micro-organism implicated in some spondyloarthropathies) from the genital mucosa does not require Fas mediated apoptosis.11
Our results suggest that there is no involvement of apoptosis via a Fas/Fas L pathway in AS.
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