title: Intrathecal soluble HLA-E correlates with disease activity in patients with multiple sclerosis and may cooperate with soluble HLA-G in the resolution of neuroinflammation.
abstract: Expression and function of the immunoregulatory molecule HLA-E was investigated in patients with relapsing-remitting (RR) multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) soluble (s)HLA-E and -G levels were measured by ELISA in 80 RRMS patients. Controls were patients with other inflammatory neurological disorders (OIND, n = 81) and noninflammatory neurological disorders (NIND, n = 86). Serum sHLA-E concentrations were higher in RRMS than in NIND patients only. CSF sHLA-E concentrations were higher in RRMS than controls. Increased CSF sHLA-E levels were detected in MRI inactive and clinically stable RRMS patients. sHLA-E intrathecal synthesis (ITS) was higher in RRMS than controls, and the number of patients with sHLA-E ITS above cut-off was higher i) in MS than controls, and ii) in clinically stable than clinically active MS patients. sHLA-E CSF levels and ITS correlated with i) the same sHLA-G parameters, and ii) disease duration. HLA-E expression and co-expression with CD markers were investigated in MS plaques from three different cases by immunohistochemistry and confocal microscopy, respectively. Infiltrating T lymphocytes and macrophages, as well as resident microglial cells and astrocytes expressed HLA-E. CSF samples from MS patients were finally tested for inhibitory activity of in vitro CTL and NK cell mediated cytotoxicity. sHLA-E⁺ were more effective than sHLA-E⁻ CSF samples in such inhibition. Maximum inhibition was achieved with sHLA-E⁺/sHLA-G⁺ CSF samples In conclusion, increased sHLA-E CSF levels may play an immunomodulatory role in MS, contributing to the inhibition of intrathecal inflammatory response. The potential of sHLA-E as biomarker of MS activity warrants further investigation.
authors.affiliation: Laboratory of Oncology, Instituto Giannina Gaslini, Via Gaslini 1, 16148 Genoa, Italy. fabiomorandi@ospedale-gaslini.ge.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.forename: Consuelo
authors.initials: C
authors.lastname: Venturi
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Castellazzi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Baldi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Caniatti
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Tola
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.forename: Enrico
authors.initials: E
authors.lastname: Fainardi
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D059951:HLA-G Antigens / Q000097:blood / Q000134:cerebrospinal fluid*; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000134:cerebrospinal fluid*; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D013129:Spinal Puncture; D000097625:HLA-E Antigens
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens