Potential role of soluble human leukocyte antigen-G molecules in multiple sclerosis.
Nonclassical human leukocyte antigen (HLA)-G antigens in soluble form (sHLA-G) have recently been suggested to have a potential role as immunomodulatory factors in multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system of unknown etiology and supposed autoimmune origin. In MS patients, sHLA-G levels were elevated in cerebrospinal fluid (CSF), intrathecally synthesized, predominantly represented by the HLA-G5 isoform and even more elevated in cases of inactive disease, as determined by magnetic resonance imaging. In MS, CSF sHLA-G concentrations were also related to the formation of an intrathecal anti-inflammatory microenvironment based on a positive correlation to CSF interleukin-10 titers and an inverse association to the levels of antiapoptotic sFas molecules in the CSF. Expression of HLA-G antigens was detected in microglia, macrophages, and endothelial cells within and around MS lesions and was enhanced in microglial cells by T-helper-1 proinflammatory cytokines. A novel subpopulation of naturally occurring CD4(+) and CD8(+) regulatory T cells expressing HLA-G1 and secreting HLA-G5 was identified in the CSF of MS patients. Taken together, these findings seem to indicate that sHLA-G antigens may be implicated in the termination of MS autoimmunity and associated with remission of the disease through their function as anti-inflammatory molecules. However, the mechanisms operating in the immunomodulatory circuit mediated by sHLA-G proteins remain to be clarified.
Fainardi
Enrico
E
Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S Anna, Ferrara, Italy. henryfai@tin.it
Rizzo
Roberta
R
Castellazzi
Massimiliano
M
Stignani
Marina
M
Granieri
Enrico
E
Baricordi
Olavio Roberto
OR
D015551:Autoimmunity / Q000276:immunology; D006680:HLA Antigens / Q000134:cerebrospinal fluid / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000134:cerebrospinal fluid; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor / Q000134:cerebrospinal fluid
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D019014:fas Receptor; D016753:Interleukin-10