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

Fabio Morandi, Consuelo Venturi, Roberta Rizzo, Massimiliano Castellazzi, Eleonora Baldi, Maria Luisa Caniatti, Maria Rosaria Tola, Enrico Granieri, Enrico Fainardi, Antonio Uccelli, Vito Pistoia

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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.

Original languageEnglish
Pages (from-to)944-955
Number of pages12
JournalJournal of NeuroImmune Pharmacology
Volume8
Issue number4
DOIs
Publication statusPublished - Sep 2013

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Keywords

  • HLA-E
  • Immunomodulation
  • Multiple sclerosis
  • Neuroinflammation

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

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