Neuropediatrics 2012; 43 - PS17_07
DOI: 10.1055/s-0032-1307134

mRNA-expression patterns of Fas and its signalling cascade in Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)

R Hofmann 1, S Tietz 2, T Thomas 2, R Reuss 2, P Oschmann 3, M Berghoff 2
  • 1Abteilung Neuropädiatrie, Sozialpädiatrie und Epileptologie, Gießen, Germany
  • 2Klinik für Neurologie, Gießen, Germany
  • 3Neurologische Klinik der Klinikum Bayreuth GmbH, Bayreuth, Germany

Aims: Recent studies showed that Fas expression in leukocytes differs during the course of disease in MS. Fas can regulate a chronic immune response by inducing apoptosis through FADD and Caspase 8. Binding of cFlip instead of Caspase 8 changes the signalling towards survival. Our objective was to characterize the mRNA-expression levels of Fas, FADD, Caspase 8 and cFlip in peripheral blood mononuclear cells in relapsing-remitting (RR) MS and in leukocytes from the spleen and the CNS in EAE.

Methods: mRNA levels were quantified by using SYBR-Green Real-Time PCR. RR-MS patients were studied in relapse and 3 month after relapse (remission) and compared to a baseline group with no clinical activity and healthy controls (HC). None of the patients were on immunomodulatory therapy. C57Bl/6 mice were immuniced with MOG35–55 and sacrificed during the course of disease at day 8, 16 and 24.

Results: In MS, Fas and Caspase 8 mRNA expressions were decreased during the course of disease and showed a negative correlation with the severity of symptoms. The transcripts of FADD were increase in all patients groups. There was no significant change in cFlip mRNA expression in MS. In EAE, the transcripts of Fas did not differ within the spleen, but were increased in cerebral leukoytes at day 24. FADD mRNA expressions in EAE were increased in the spleen, but were decreased in the leukocytes from the CNS. There was no significant change in cFlip mRNA expression in the spleen, but cerebal leukocytes showed an increase of cFlip transcripts at day 8 and 16. The transcripts of Caspase 8 were decreased in EAE in leukocytes from the spleen, but were increased at day 16 and 24 in the CNS.

Conclusion: In MS, the transcripts of the proteins are decreased that are known to regulate a chronic immune response through apoptosis and thus might prolong disease activity. In EAE, Fas and Caspase 8 are up regulated in the CNS during remission. Therefore the transcripts of the proteins are increased that induce apoptosis. This might contribute to the termination of the immunresponse in autoreaktive leukocytes in the CNS.

Multiple Sclerosis - Experimental Autoimmune Encephalomyelitis - Relapse