The main objective is to explore the efficacy and safety of Telitacicept in the treatment of refractory/recurrent anti-NMDAR and anti-LGI1 encephalitis.

Through this prospective, single-center, open-label clinical trial, we aim to investigate the effectiveness and safety of Telitacicept in refractory/recurrent anti-NMDAR and anti-LGI1 encephalitis by add-on therapy of Telitacicept combined with traditional treatment.

Inclusion Criteria:

1. Age ≥14 years old, male or female;

2. Symptoms of autoimmune encephalitis (AE) ≤ 9 months prior to enrollment;

3. Diagnosed as autoimmune encephalitis, diagnostic criteria as follows:

   1. Rapid onset (<3 months) of at least four of the following six major symptoms:

      • Abnormal (mental) behavior or cognitive dysfunction
      • Speech dysfunction (verbal urgency, hypospeech, mutism)
      • Seizures
      • Movement disorders, dyskinesias, or postural rigidity/abnormalities
      • Decreased level of consciousness
      • Autonomic dysfunction or central hypoventilation in the presence of one or more of the six major symptoms;

   2. Positive anti-NMDAR (GluN1) IgG antibody detected in CSF or positive serum and/or cerebrospinal fluid LGI1 antibody; c．Reasonable exclusion of other etiologies and other well-defined encephalitis syndromes (e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary CNS vasculitis, Rasmussen encephalitis);

4. Refractory AE: ineffective treatment with steroids and rituximab or other immunosuppressants, post-treatment mRS score≥2 (stable for at least 24 hours）;Recurrent AE: at least 2 months after 1st or 2nd line treatment, new symptoms or worsening of existing symptoms (mRS increase>1); 5）Doses of steroids and other immunosuppressants (e.g. azathioprine, mycophenolate mofetil, cyclophosphamide) should be stabilised for 4 weeks prior to enrolment; 6）Ability to obtain patient or proxy consent; 7）Women of childbearing potential should use effective contraception during treatment or avoid heterosexual intercourse for at least 3 months after the last dose of talitacicept;

Exclusion Criteria:

1. History of other autoimmunity such as SLE, RA, SS. Patients with hyperthyroidism and hypothyroidism cannot be excluded;

2. Abnormal laboratory indicators, including but not limited to the following indicators:

   White blood cell count<3×10^9 /L Neutrophil count<1.5×10^9 /L Hemoglobin<85g/L Blood platelet count<80×10^9 /L Serum creatinine>1.5×ULN TBil(total bilirubin) >1.5×ULN ALT>3× ULN AST>3× ULN Alkaline phosphatase>2× ULN Creatine kinase>5× ULN

3. Evidence of active infection such as shingles, HIV or active tuberculosis, etc.

4. Currently have active hepatitis or have severe liver disease and a history of it.

   • Patiens with abnormal Hepatitis B test as follows should be excluded: HbsAg positive; HbsAg negative but HbcAb positive, and HBV-DNA positive. Whereas patients with HbsAg negative but HbcAb positive, and HBV-DNA negative can be included.
   • Exclude patients who are positive for hepatitis C antibodies ;

5. Uncontrolled diabetes mellitus: Glycosylated hemoglobin>9.0% or fasting blood glucose≥11.1mmol/L;

6. Received any live vaccine within 3 months prior to enrollment or planned to receive any vaccine during the study;

7. Received rituximab or other biological therapies within 1 month prior to enrollment;

8. Malignancy;

9. Allergic to human biological products;

10. Participated in any clinical trial within 28 days prior to enrollment or within 5 times the half-life of the investigational drug participating in the clinical trial

11. Patients who plan to have children during the trial, or who are pregnant or breastfeeding;

12. Alcohol or drug abuse/addiction is known to have an impact on compliance with trial requirements;

13. Patients who are deemed unsuitable for the trial by the investigator (e.g., those with severe mental disorders).