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Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis

Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy, Department of Neurosciences, Section of Neuroradiology, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy, henryfai{at}tin.it

R Rizzo

Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

L Melchiorri

Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

M Castellazzi

Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

E Paolino

Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

M R Tola

Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

E Granieri

Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

O R Baricordi

Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy, Department of Experimental and Diagnostic Medicine, Biotechnology Center, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (p<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (p<0.02) and MRI active (p<0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (p<0.01) and MRI stable (p<0.001) MS. sHLA-I levels were low in the serum of clinically active (p<0.001) and high in the CSF of MRI active (p<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (p<0.01) and increased in the CSF of MRI inactive MS (p<0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.

Key Words: cerebrospinal fluid • intrathecal synthesis • multiple sclerosis • sHLA-G • sHLA-I

Multiple Sclerosis, Vol. 12, No. 1, 2-12 (2006)
DOI: 10.1191/1352458506ms1241oa


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