CSF levels of soluble HLA-G and Fas molecules are inversely associated to MRI evidence of disease activity in patients with relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) concentrations of soluble HLA-I (sHLA-I), HLA-G (sHLA-G) and anti-apoptotic Fas (sFas) molecules were measured by ELISA technique in 65 relapsing-remitting Multiple Sclerosis (RR MS) patients classified according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Sixty-four patients with other inflammatory neurological disorders (OIND) and 64 subjects with non-inflammatory neurological disorders (NIND) served as controls. CSF concentrations were higher in RR MS and in OIND than in NIND patients for sHLA-I (p < 0.02), greater in RR MS than in OIND and in NIND for sHLA-G (p < 0.001 and p < 0.01, respectively), and lower in RR MS than in OIND and in NIND for sFas (p < 0.001 and p < 0.02, respectively). An increase in CSF levels was identified in MRI active RR MS for sHLA-I (p < 0.01) and in MRI stable RR MS for sHLA-G (p < 0.01), whereas CSF values of sFas were decreased in RR MS without Gd enhancing lesions (p < 0.02). In MS patients without MRI disease activity, a trend towards an inverse correlation was found between CSF concentrations of sHLA-G and sHLA-I and between CSF levels of sHLA-G and sFas. Our results indicate that enhanced CSF levels of sHLA-I antigens most likely represent an indirect manifestation of intrathecal immune activation taking place in neuroinflammation. Conversely, reciprocal fluctuations in CSF sHLA-G and sFas levels observed when MRI disease activity resolved suggest that sHLA-G could play an immuno-modulatory role in MS through Fas/FasL-mediated mechanisms