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 human leukocyte antigen class I (HLA-I) (sHLA-I), HLA-G (sHLA-G) and anti-apoptotic Fas (sFas) molecules were measured by enzyme linked immunosorbent assay technique in 65 relapsing-remitting (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 noninflammatory neurological disorders (NIND) served as controls. CSF concentrations were higher in RRMS and in OIND than in NIND patients for sHLA-I (P < 0.02), greater in RRMS than in OIND and in NIND for sHLA-G (P < 0.001 and P < 0.01, respectively) and lower in RRMS 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 RRMS for sHLA-I (P < 0.01) and in MRI stable RRMS for sHLA-G (P < 0.01), whereas CSF values of sFas were decreased in RRMS without Gd-enhancing lesions (P < 0.02). In MS patients with no evidence of 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 immunomodulatory role in MS through Fas/FasL-mediated mechanisms.