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Autor(en) / Beteiligte
Titel
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
Ist Teil von
  • Journal of neuroimmune pharmacology, 2013-09, Vol.8 (4), p.944-955
Ort / Verlag
Boston: Springer US
Erscheinungsjahr
2013
Link zum Volltext
Quelle
SpringerLink
Beschreibungen/Notizen
  • 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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