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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

Fingerprint

HLA-G Antigens
Multiple Sclerosis
Cerebrospinal Fluid
Nervous System Diseases
Relapsing-Remitting Multiple Sclerosis
Serum
Confocal Microscopy
Astrocytes
Natural Killer Cells
Biomarkers
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Macrophages
T-Lymphocytes

Keywords

  • HLA-E
  • Immunomodulation
  • Multiple sclerosis
  • Neuroinflammation

ASJC Scopus subject areas

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

Cite this

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

In: Journal of NeuroImmune Pharmacology, Vol. 8, No. 4, 09.2013, p. 944-955.

Research output: Contribution to journalArticle

Morandi, Fabio ; Venturi, Consuelo ; Rizzo, Roberta ; Castellazzi, Massimiliano ; Baldi, Eleonora ; Caniatti, Maria Luisa ; Tola, Maria Rosaria ; Granieri, Enrico ; Fainardi, Enrico ; Uccelli, Antonio ; Pistoia, Vito. / 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. In: Journal of NeuroImmune Pharmacology. 2013 ; Vol. 8, No. 4. pp. 944-955.
@article{8ac68b039fe147f3a49bf070f7798541,
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.",
keywords = "HLA-E, Immunomodulation, Multiple sclerosis, Neuroinflammation",
author = "Fabio Morandi and Consuelo Venturi and Roberta Rizzo and Massimiliano Castellazzi and Eleonora Baldi and Caniatti, {Maria Luisa} and Tola, {Maria Rosaria} and Enrico Granieri and Enrico Fainardi and Antonio Uccelli and Vito Pistoia",
year = "2013",
month = "9",
doi = "10.1007/s11481-013-9459-3",
language = "English",
volume = "8",
pages = "944--955",
journal = "Journal of NeuroImmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - 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

AU - Morandi, Fabio

AU - Venturi, Consuelo

AU - Rizzo, Roberta

AU - Castellazzi, Massimiliano

AU - Baldi, Eleonora

AU - Caniatti, Maria Luisa

AU - Tola, Maria Rosaria

AU - Granieri, Enrico

AU - Fainardi, Enrico

AU - Uccelli, Antonio

AU - Pistoia, Vito

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - HLA-E

KW - Immunomodulation

KW - Multiple sclerosis

KW - Neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=84882246495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882246495&partnerID=8YFLogxK

U2 - 10.1007/s11481-013-9459-3

DO - 10.1007/s11481-013-9459-3

M3 - Article

VL - 8

SP - 944

EP - 955

JO - Journal of NeuroImmune Pharmacology

JF - Journal of NeuroImmune Pharmacology

SN - 1557-1890

IS - 4

ER -