Clinical and immunological analysis of mycophenolate mofetil treatment in anti-leucine-rich glioma-inactivated 1 encephalitis

Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis by analyzing the clinical and immunologic data of patients treated with MMF in this prospective cohort of anti-LGI1 encephalitis. Methods Patients treated with MMF for more than one year in Peking Union Medical College Hospital were included in this study. MMF was given at a dosage of 1.5-3.0 g/d in the induction period (two to four months) and 0.75-2.00 g/d in the maintenance period. All the patients were followed up regularly. Modified Rankin Scale (mRS) score evaluation, serum IgG and peripheral CD19-positive B cells, CD4-positive T cells and CD8-positive T cells testing were performed every two months. Results Fifteen patients were included in this study who received first-line immunotherapy combined with MMF. No other second-line therapy including rituximab was used. Thirteen patients responded well to MMF combined with first-line immunotherapy (a decrease in mRS score of more than 1). All 15 patients had a good outcome (i.e., a mRS score of 0-2), including nine patients without residual symptoms (a mRS score of 0). After 12 months of MMF treatment, CD19-positive B cells were significantly decreased (median 320 (227, 628)×106/L vs 152 (105, 223)×106/L; Z=-2.028, P=0.043), while serum IgG (9.07 (6.70, 11.32) g/L vs 8.35 (6.63, 10.69) g/L, P=0.144)), CD4-positive T cells (1 136 (736, 1 432)×106/L vs 1 055 (802, 1 072)×106/L, P=0.866) and CD8-positive T cells (627 (413, 784)×106/L vs 568 (393, 743)×106/L, P=0.735) were not significantly changed. Three patients relapsed and were treated with additional cycle of first-line immunotherapy and increased dosage of MMF (induction dosage) resulting in remission. CD19-positive B cells were tested to be increased during the patients′ relapse. No serious adverse event was noted in all these patients. Conclusions MMF is safe and effective as a long-term immunotherapy in patients with anti-LGI1 encephalitis. MMF can be used as an add-on therapy to first-line immunotherapy for autoimmune encephalitis. CD19-positive B cell count should be monitored and used as a parameter to individualize dosage of MMF. Key words: Encephalitis; Autoimmunity; Anti-leucine-rich glioma-inactivated 1; Mycophenolate mofetil; Immunotherapy; B-Lymphocytes