Associations of serum soluble Fas and Fas ligand (FasL) with outcomes in systemic lupus erythematosus

Abstract

ObjectiveFas/Fas ligand (FasL) and B cell-activating factor (BAFF) signalling have pivotal roles in SLE pathogenesis. We investigated the clinical associations of serum concentrations of soluble Fas (sFas) and soluble FasL (sFasL) in SLE and their relationship with BAFF.MethodsSerum sFas and sFasL were quantified by multiplex assay, and BAFF by ELISA, in 118 patients with SLE and 17 healthy controls (HC). SLE disease activity and organ damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index.ResultssFas, sFasL and BAFF were detectable in all samples. Serum sFas and sFasL were significantly higher in SLE compared with HC. In univariable regression analyses, patients with active renal disease and those with flare had significantly higher levels of sFas compared with those without. High serum BAFF in patients with SLE was associated with increased sFas but not sFasL. The association between sFas and renal disease remained significant after adjusting for BAFF, but the association with flare attenuated. High sFas levels were associated with increased time-adjusted mean SLEDAI-2K, even after adjusting for BAFF, and with higher odds of flare over time. In contrast, high sFasL was associated with reduced organ damage over time. Serum sFasL/sFas ratio was negatively associated with active overall disease, flare and organ damage.ConclusionsSerum sFas is associated with active renal SLE, and active disease and flare over time, while sFasL/sFas ratio is negatively associated with disease activity and organ damage accrual. Treatments correcting abnormal levels of sFas/FasL may be worthy of evaluation in SLE.

Soluble CD95L in cancers and chronic inflammatory disorders, a new therapeutic target?

“…While in Sjögren's syndrome, the immune system targets mainly salivary and tear glands engendering dryness in the eyes and mouth, these diseases can affect other organs including skin, kidneys, articulations, lungs, and brain. In Lupus and SS, accumulating evidence points to s-CD95L as a pivotal effector of the disease aggressiveness [6,102], with a recent study confirming that s-CD95L levels were higher in lupus patients [103]. We previously observed that s-CD95L concentrations were associated with the disease progression in lupus patients, and that this ligand promoted the Th17 trafficking in inflamed organs [4,5].…”

Soluble FAS Ligand directs human memory B cells towards antibody-secreting cells

“…In addition, patients with more severe rheumatoid arthritis have higher sFASL levels in synovial fluid compared to those with less severe pathology [41][42][43] . These autoimmune diseases are all characterized by the presence of autoantibodies, produced by ASCs originating from self-reactive B cells.…”

Baseline Ratio of Soluble Fas/FasL Predicts Onset of Pulmonary Hypertension in Elder Patients Undergoing Maintenance Hemodialysis: A Prospective Cohort Study

“…Furthermore, the ratio of sFas/sFasL has also been identified as a marker for vascular dysfunction or vasculopathy ( Adly et al, 2016 ). sFas and/or sFasL has been identified the association with tumor, coronary artery disease, rheumatic disease, and other diseases ( Sahinarslan et al, 2012 ; Adly et al, 2016 ; Chiloff et al, 2020 ; Vincent et al, 2020 ). However, the roles of sFas, sFasL and their ratio in PH with ESRD who undergoing hemodialysis (especially in elder patients) have not been identified.…”