Autoimmune Encephalitis After Japanese Encephalitis In Children:A Prospective Study

Obgective:To investigate whether the patients with autoimmune encephalitis after Japanese encephalitis(JE)exist other known autoimmune encephalitis antibodies except anti-N-methyl-D-aspartate receptor(NMDAR)antibodies,and analyze the clinical characteristics of the patients.Method:We detected the known autoimmune encephalitis antibodies in the serum and cerebrospinal fluid(CSF)of JE patients within one week of symptom onset by indirect immunofluorescence.The known autoimmune encephalitis antibodies in the serum were detected on day 21 post-JE again.If the patients relapsed during the convalescent phase,they would be admitted to hospital again and had reexaminations such as brain MRI and Japanese encephalitis virus PCR and detection for the known autoimmune encephalitis antibodies in the serum and CSF.And if autoimmune encephalitis antibodies were positive in the CSF,the diagnosis of autoimmune encephalitis was confirmed,immunotherapy would be conducted to them.Results:1.All 31 patients were negative for the known autoimmune encephalitis antibodies at the onset of JE in the serum and CSF;2.On day21 post JE onset,two patients with biphasic pattern and one patient with single-phase pattern were positive for serum anti-NMDAR-Ig G,while the other 28 patients were negative for the detection of known autoimmune encephalitis antibodies;3.During the convalescent phase,five patients developed autoimmune encephalitis(two had anti-NMDAR antibodies,one had anti-γ-aminobutyric acid B receptor[GABA_BR]antibodies,and two were negative for the known autoimmune encephalitis antibodies);4.Compared to the patients with anti-NMDAR encephalitis after JE,the patients with anti-GABA_BR encephalitis had lower number of white blood cells in cerebrospinal fluid,less obvious changes of cranial imaging,and better prognosis.Conclusion:1.The detection for the known autoimmune encephalitis antibodies of 31 patients with JE at the onset of JE were negative;2.Serum anti-NMDAR-Ig G test positive on day 21 post JE onset does not necessarily result in anti-NMDAR encephalitis;3.Anti-GABA_BR antibodies can be detected in the patients with autoimmune encephalitis after JE;4.The severity and prognosis of autoimmune encephalitis mediated by different autoantibodies may vary after Japanese encephalitis virus infection.Obgective:To investigate whether there are other unknown autoimmune encephalitis antibodies in serum or CSF of patients with autoimmune encephalitis after JE,although their known autoimmune encephalitis antibody detection were negative,and analyze the clinical characteristics of the patients.Method:We detected the unknown autoimmune encephalitis antibodies in the serum and CSF of JE patients within one week of symptom onset from part one by immunohistochemistry and immunofluorescence.The unknown autoimmune encephalitis antibodies in the serum were detected on day 21post-JE again.If the patients relapsed during the convalescent phase,they would be detected the unknown autoimmune encephalitis antibodies in the serum and CSF a third time.We collected patients’ data and analyzed their clinical characteristics.Results:1.All 31 patients were negative for the unknown autoimmune encephalitis antibodies at the onset of JE in the serum and CSF;2.On day21 post JE onset,one patient with single-phase pattern were positive for serum unknown autoimmune encephalitis antibodies,while the other 30 patients were negative for the detection of unknown autoimmune encephalitis antibodies;3.Two of five patients who developed autoimmune encephalitis were positive for the unknown autoimmune encephalitis antibodies;4.Compared to the patients with anti-NMDAR encephalitis,the patients with unknown antibody-mediated autoimmune encephalitis had relatively mild clinical symptoms,lower number of white blood cells and protein in cerebrospinal fluid,smaller lesion range of brain MRI and less neurological defects during the follow-up.Conclusion:1.The detection for the unknown autoimmune encephalitis antibodies of 31 patients with JE at the onset of JE were negative;2.Detection of serum autoimmune encephalitis antibodies on day 21 post JE onset is of low predictive value for the occurrence of autoimmune encephalitis;3.In addition to the known autoimmune encephalitis antibodies,unknown autoimmune encephalitis antibodies can trigger autoimmune encephalitis following JE;4.Compared to the patients with anti-NMDAR encephalitis after JE,the patients with unknown antibody-mediated autoimmune encephalitis had lighter clinical symptoms and better prognosis.Obgective : To investigate the immune mechanisms of autoimmune encephalitis after JE,analyze the clinical significance of cytokines in the disease,follow up and analyze the long-term outcomes.Method:We detected cytokines in the serum and CSF of JE patients within one week of symptom onset from part one by enzyme linked immunosorbent assay(ELISA),including matrix metalloproteinase-9(MMP-9),C-X-C motif ligand 13(CXCL13),B cell activating factor(BAFF),C-X-C motif ligand 10(CXCL10),and interleukin-6(IL-6).The cytokines in the serum were detected on day 21 post-JE again.If the patients relapsed during the convalescent phase,they would be detected the cytokines in CSF a third time.We respectively assessed the neurological function of all patients using the modified Rankin Scale(m RS),at the1-month,2-month,6-month,and 12-month follow-ups.Results:1.During the acute phase,there were no significant differences in the level of CXCL13,BAFF,CXCL10,IL-6,or MMP-9 in the serum and CSF between the patients who developed autoimmune encephalitis and those who did not(p > 0.05 for all);2.For the patients who developed autoimmune encephalitis,the levels of serum CXCL13 and IL-6 were significantly increased on day 21 post-JE onset compared to that in the acute phase(p < 0.05);the levels of CXCL13,BAFF,CXCL10,and MMP-9 in the CSF were significantly increased at the onset of autoimmune encephalitis symptoms compared with that in the acute phase(p < 0.05);3.The levels of MMP-9,CXCL10,and IL-6 in the serum were significantly decreased on day 21 post-JE onset compared with that in the acute phase in the patients who did not develop autoimmune encephalitis(p < 0.05);4.At the 12-month follow-up,the patients who developed autoimmune encephalitis had a greater number of neurological deficits(median m RS 2[IQR 1-2] vs 1 [0-2];p = 0.044)than those who did not.Conclusion:1.The serum and CSF level of cytokines at JE onset may not be used as predictors of autoimmune encephalitis after JE;2.The serum level of CXCL13 on day 21 post-JE onset may represent an appropriate predictor of autoimmune encephalitis after JE;3.The patients who developed autoimmune encephalitis after JE had poorer long-term outcomes compared to those who did not.