Auto-antibodies in adult herpes encephalitis

cancelled 750 Posters, Monday 10 September © 2012 EFNS European Journal of Neurology 19 (Suppl. 1), 458–807 P2810 Viral load, cytokine storm, TNF-α and TNF-α promoter polymorphism as possible predictors for disease progression in Japanese encephalitis S.K. Pujhari1, R.K. Ratho1, S. Prabhakar2, B.M. Mishra1, M. Modi2 1Virology, 2Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Japanese encephalitis (JE) is an important arboviral infection of public health concern. JE manifests with a selflimited febrile illness to severe encephalitis. As the disease pathogenesis is poorly understood, study on cytokine profiles (Th1 and Th2), viral load on disease severity and TNF-α promoter polymorphism as host genetic makeup were undertaken. 227 patients with acute encephalitic syndrome, 126 febrile illness suspected of JE and 79 apparently healthy individuals as control were enrolled. JE cases were diagnosed with IgM captured ELISA and RT-PCR. 88 (54.7%) encephalitis patients, 50 (39.7%) febrile illness cases were diagnosed as JE and 50 (63.3%) controls had JE specific IgG antibodies. Bioinformatics analysis revealed JEV genotype III as circulating strain and a novel S227T mutation in domain III of E gene. Significantly high viral load was detected in severe JE patients than in those with milder encephalitis (43,349 vs. 8,721 mean copies/ml). Interestingly, significant levels of TNF-α (>55pg/ml cut-off) and IL-6 ( >370pg/ml cut-off) in encephalitis due to JE and IFN-γ in febrile JE patients without encephalitis were observed. Th1 shift (IFN-γ /IL-4: >1) was observed in encephalitis patients. TNF-α promoter polymorphism analysis revealed significant distribution of -308A and -863C alleles in encephalitis group more so among 7 out of 9 patients died from this group having the same allelic distribution. Th1 cytokine shift; higher levels of viral load, IL-6 and TNF-α and significant distribution of -308A and -863C alleles of TNF-α promoters are possible major contributors of severity and mortality among Japanese encephalitis cases. P2811 Intrathecal transplantation of adult neural stem/precursor cells dampens the effector phase of experimental auto-immune encephalomyelitis D. De Feo, C. Laterza, A. Merlini, E. Brambilla, F. Ruffini, G. Comi, G. Martino Institute of Experimental Neurology, Università VitaSalute San Raffaele, IRCCS San Raffaele, Milan, Italy Introduction: Neural stem/precursor cell (NPC) transplantation ameliorates disease severity in experimental auto-immune encephalomyelitis (EAE) through bystander neuroprotective and immunomodulatory effects. We investigated how NPCs directly transplanted in the cerebrospinal fluid interfere with the CNS-infiltrating immune effector cells that sustain neuroinflammation. Methods: Chronic EAE was induced in C57 Bl/6 mice by immunization with the MOG 35-55 peptide. At the peak of the disease, 20 mice per group were transplanted in the cisterna magna by stereotaxic injection of GFP-labelled adult NPCs or vehicle. The in vivo characterization of transplanted NPCs was assessed by immunofluorescence and ex vivo analysis of CNS inflammatory infiltrate was performed by flow cytometry. Results: After 40 days post-immunization (dpi), transplanted NPCs persisted almost exclusively within the perivascular inflammatory infiltrate and around 70% retained an undifferentiated phenotype. NPC-transplanted mice showed a persistent amelioration of disease severity when compared with sham-treated mice in terms of clinical score (1.1±0.25 improvement at 80 dpi p<0.02), demyelination (57%, p<0.05) and axonal loss (750%, p<0.02). Moreover, at 40 dpi we observed in NPCtransplanted mice a quantitative reduction of infiltrating myeloid dendritic cells (58.92% reduction, p<0.01), macrophages (34.02% reduction, p<0.01) and T-cells (24.97% reduction, p<0.05), in particular Th17 (35.98% reduction, p<0.01) and Th1 (36.62% reduction, p<0.01) effector cells. Conclusion: This work confirms the efficacy of intrathecal transplantation of adult NPCs in ameliorating disease severity in experimental multiple sclerosis and suggests that transplanted NPCs target the CNS-restricted pathogenic phase of neuroinflammation.