Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies

Abstract

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients’ expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.