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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

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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.

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Acknowledgments

We thank Mrs. Camilla Valentino for excellent secretarial assistance. This work have been supported by Ministero del Lavoro, della Salute e delle Politiche Sociali (Progetti di Ricerca Corrente) and by Research Program Regione Emilia Romagna - University 2007–2009, (Innovative Research) - code PRUa1a-2007–008. The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Oncology, Instituto Giannina Gaslini, Via Gaslini, 1, 16148, Genoa, Italy

    Fabio Morandi & Vito Pistoia

  2. Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy

    Consuelo Venturi & Antonio Uccelli

  3. Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Ferrara, Italy

    Roberta Rizzo

  4. Multiple Sclerosis Center, Section of Neurology, Department of Medical and Surgical Sciences of the Communication and Behaviour, University of Ferrara, Arcispedale S. Anna, Ferrara, Italy

    Massimiliano Castellazzi & Enrico Granieri

  5. Department of Biochemistry and Molecular Biology, Section of Biochemistry and Clinical Biochemistry, University of Ferrara, Ferrara, Italy

    Massimiliano Castellazzi

  6. Multiple Sclerosis Center, Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy

    Eleonora Baldi, Maria Luisa Caniatti & Maria Rosaria Tola

  7. Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy

    Enrico Fainardi

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  1. Fabio Morandi
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  2. Consuelo Venturi
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  3. Roberta Rizzo
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  4. Massimiliano Castellazzi
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  5. Eleonora Baldi
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  6. Maria Luisa Caniatti
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  7. Maria Rosaria Tola
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  8. Enrico Granieri
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  9. Enrico Fainardi
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  10. Antonio Uccelli
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  11. Vito Pistoia
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Correspondence to Fabio Morandi.

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Morandi, F., Venturi, C., Rizzo, R. et al. 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. J Neuroimmune Pharmacol 8, 944–955 (2013). https://doi.org/10.1007/s11481-013-9459-3

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  • DOI: https://doi.org/10.1007/s11481-013-9459-3

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