Elevated levels of soluble Fas (APO-1, CD95), soluble Fas ligand, and matrix metalloproteinase-3 in sera from patients with active untreated adult onset Still’s disease

Abstract

To investigate serum levels of soluble Fas (sFas), soluble Fas ligand (sFas-L), and matrix metalloproteinase-3 (MMP-3) in patients with active untreated adult onset Still's disease (AOSD). Serum levels of sFas, sFas-L, and MMP-3 were determined by enzyme-linked immunosorbent assays in 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Linear regression was used to evaluate the correlation between clinical activity scores and serum levels of sFas, sFas-L, and MMP-3 in AOSD patients. Significantly higher levels of sFas, sFas-L, and MMP-3 in sera were found in active untreated AOSD patients compared to healthy controls. Serum levels of sFas, sFas-L, and MMP-3 correlated well with clinical activity scores of AOSD patients (r=0.467, 0.694, and 0.798, respectively). There was a significant correlation between CRP values and serum levels of sFas-L as well as MMP-3 (r=0.583 and r=0.582, respectively, both p<0.01), and a positive correlation between serum sFas-L levels and serum MMP-3 levels (r=0.726, p<0.001) in AOSD patients. Significantly higher levels of serum sFas-L were found in AOSD patients than in RA patients. Serum levels of sFas, sFas-L, and MMP-3 fluctuated and were found to be parallel to disease activity of AOSD. sFas, sFas-L, and MMP-3, which were significantly elevated in sera of active untreated AOSD patients and paralleled disease activity, may be involved in the pathogenesis of this disease. Further studies are needed to determine the pathophysiologic role of sFas, sFas-L, and MMP-3 in AOSD.

Adult-Onset Still’s Disease: From Pathophysiology to Targeted Therapies

“…This hypothesis is also supported by raised Fas and FasL levels in untreated AOSD patients compared to healthy controls [50]. …”

Chronic Adult-Onset Still’s Disease With Positive Antinuclear Antibodies: Navigating Diagnostic Dilemmas and Clinical Implications

“…Globally, the illness primarily affects young adults (the median age at diagnosis is approximately 36 years) [ 7 , 8 ]; but cases have been reported as late as 83 years [ 9 , 10 ]. While the exact cause of AOSD remains unknown, researchers have identified elevated levels of certain inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-18 (IL-18), in individuals with the condition [ 5 ]. These elevated markers are believed to contribute to the systemic inflammation seen in AOSD.…”

“…While no specific diagnostic laboratory test exists, serum ferritin levels can aid in monitoring and considering AOSD [ 4 ]. Treatment primarily consists of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and rheumatological agents [ 5 ]. Negative antinuclear antibody (ANA) and Rheumatoid (RA) factor are included as part of the minor criteria for diagnosing AOSD; however, rare cases with positive ANA and no other features of systemic lupus erythematosus (SLE) or other autoimmune disorders have been reported, suggesting that a positive ANA or RA factor does not rule out the diagnosis of AOSD [ 6 ].…”

Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra

“…Apoptosis in patients with autoimmune disease is considered an essential mechanism to counterbalance the abnormal immune response and to maintain immunologic tolerance (5,6). Although cell proliferation is exaggerated in the synovial membrane of patients with RA, studies have shown increased levels of synovial and serum Fas and FasL in these patients likely due to the enhanced inflammatory and oxidative burden on infiltrating mononuclear cells and circulating T lymphocytes (7)(8)(9).…”