1. The Clinical And Immunological Indicators Of Mycophenolate In The Treatment Of Autoimmune Encephalitis 2. The Application Value Of Cytokine Detection In The Diagnosis And Treatment Of Anti-N-methyl-D-aspartate Receptor Encephalitis

Objective:Autoimmune encephalitis(AE)is a cluster of encephalitis mediated by autoantibodies targeting neuro-surface antigens and responsive to immunotherapy[1].Mycophenolate mofetil(MMF)is regarded as the long-term immunotherapy,mainly for relapse or refractory cases,as well as antibody-negative AE.This study is to evaluate the efficacy and safety of MMF in treating AE.Methods:35 AE patients treated with MMF were included in this study.The baseline characteristics,clinical presentation,laboratory results and treatment profile were analyzed.Neurological functional status were evaluated with modified Ranking score(mRS)at each follow-up.Results:The median mRS decreased significantly from 3.33± 1.52 before MMF treatment to 0.33±0.56 afterwards(p<0.001).29/35(82.86%)patients maintain relapse-free state during the follow-up and 35/35(100.00%)reached favorable neurological functional state(mRS≤2)at the final visit.Serum IgG level(p=0.014),peripheral CD19(+)B cell count(p=0.025)were statistically significant before and after MMF treatment while CD4(+)T cell count(p=0.808),CD8(+)T cell count(p=0.394)were not.Serum IgG level tend to reach the lowest point in 4 months after initiation of MMF management,peripheral CD19(+)B cell count level and mRS declined as with the treatment.Conclusions:MMF is a effective and safe therapy for AE.Possible mechanism of MMF in treating AE could be attributed to its selective inhibition of humoral immunity.MMF therapy usually takes 4 months to take full effect and maintenance of MMF improves the clinical outcome further.Thus we recommend a regimen composed of introduction phase and maintenance phase.Serum IgG level,peripheral CD19(+)B cell count can be used for patients’ evaluation and monitoring during the treatment.Objective:Anti-N-methyl-D-aspartate Receptor(anti-NMDAR)encephalitis is the most common type of autoimmune encephalitis(AE)associated with antibodies against neuro-surface antigens.Researches on the pathogenesis of anti-NMDAR encephalitis recently have suggested that humoral immunity plays an important role and anti-GluN1 antibodies are pathogenic.However,the upstream immunologic mechanism remains unclear.Our study measured the CSF and serum cytokine levels of anti-NMDAR encephalitis group and other control groups,aiming at evaluating the application significance of cytokine measurement in clinical practice.Methods:52 patients with definite anti-NMDAR encephalitis were included,as well as 21 patients with AQP4-positive NMO in inflammation control group and 20 patients in non-inflammation control group.CSF and serum samples were collected and stored at-60 ℃.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the concentrations of 5 different cytokines,which were CXCL13,BAFF,APRIL,IL-6 and CXCL10.Despite compared with control groups,anti-NMDAR patients’ samples werealso compared with their own paired CSF and serum collected during follow-up.We also studied the possible clinical factors correlating with CSF cytokine concentration.Statistics were analyzed using IBM SPSS V20.0.Results:(1)CSF CXCL13,CXCL10,APRIL of patients with anti-NMDAR encephalitis were significantly higer compared to non-inflammatory group(P<0.001;P=0.033,P=0.042 respectively).Significant difference of serum BAFF were noted between anti-NMDAR group and non-inflammatory group.Serum CXCL10 also showed difference among three groups.(2)CSF CXCL13,BAFF,IL-6(P=0.050;P=0.014;P=0.041,respectively)and serum BAFF(P=0.022)of patients with anti-NMDAR encephalitis were significantly higher in acute phase than and in relieving phase.(3)Age correlates with CSF CXCL13 level.CSF pleocytosis correlate with CSF IL-6 level.CXCL10 correlates with age,mRS,and treatment.Conclusions:Our study indicates that CSF CXCL13,CXCL10,APRIL of anti-NMDAR patients are significantly higher than non-inflammatory groups.CSF CXCL13,BAFF,IL-6 and serum BAFF level of acute phase are significantly higher than of relieving phase in anti-NMDAR patients.CSF CXCL13 correlates with age.CSF IL-6 concentration correlates with CSF pleocytosis.B lymphocyte activation is the core of humoral immunity response,which is often helped by Th17 cells.CSF CXCL13,CXCL10 and APRIL,as well as serum BAFF and CXCL10,are probably novel biomarkers for clinical assessment and follow-up after treatment in anti-NMDAR encephalitis.