• Subjects must meet the following eligibility criteria at screening to participate in this study.

• 1 Inclusion criteria for subjects with autoimmune encephalitis (hereinafter referred to as AE) of all subtypes 1.1.1 Subjects are able to understand the purpose and risks of the study, provide informed consent, and authorize the use of confidential health information in accordance with national and local privacy regulations.

• 1.2. Tumors or malignancies can be reasonably excluded before the baseline visit (randomization), and screening guidelines for thymoma, teratoma, and malignant tumors should be followed.

• 1.3. Both men and women are welcome, and the age at the time of providing informed consent is 18-80 years old (inclusive).

• 1.4. Meet the diagnosis of AE (according to the Chinese Autoimmune Encephalitis Diagnosis and Treatment Expert Consensus 2022 Edition): A. Clinical manifestations: acute or subacute onset (\<3 months), with one or more of the following neurological and psychiatric symptoms or clinical syndromes.

• a. Limbic system symptoms: recent memory loss, epileptic seizures, mental and behavioral abnormalities, one or more of the three symptoms.

• b. Encephalitis syndrome: clinical manifestations of diffuse or multifocal brain damage.

• c. Clinical manifestations of involvement of the basal ganglia and/or diencephalon/hypothalamus.

• d. Mental disorder, and the psychiatric specialist believes that it does not meet the non-organic disease.

• B. Auxiliary examination: one or more of the following auxiliary examination findings, or combined with related tumors.

• a. Abnormal cerebrospinal fluid: cerebrospinal fluid leukocytosis (\>5×106/L), or cerebrospinal fluid cytology shows lymphocytic inflammation, or specific oligoclonal bands are positive.

• b. Neuroimaging or electrophysiological abnormalities: MRI limbic system T2 or FLAIR abnormal signals, unilateral or bilateral, or other areas of T2 or FLAIR abnormal signals (excluding nonspecific white matter changes and stroke); or PET imaging limbic system hypermetabolism changes, or multiple cortical and/or basal ganglia hypermetabolism. Figure 1 shows the typical neuroimaging manifestations of AE patients. Abnormal electroencephalogram, manifested as focal epilepsy or epileptiform discharge (located in the temporal lobe or outside the temporal lobe), or diffuse or multifocal slow wave rhythm. In adult patients with anti-NMDAR encephalitis, abnormal delta brush waves (extreme delta brush) often correspond to prolonged hospitalization and poor prognosis.

• c. Specific types of tumors associated with AE, such as limbic encephalitis combined with small cell lung cancer, anti-NMDAR encephalitis combined with ovarian teratoma.

• C. Confirmatory experiments: positive anti-neuronal antibodies. Including NMDA-R, LGI-1, CASPR2, IgLON5, GABAA/BR, GlyR, AMPAR and axonal protein-3α and intracellular substance antibodies anti-Hu, anti-Ma2, anti-CRMP5, anti-Yo, anti-double carrier protein, anti-GAD, etc.

• D. Reasonably exclude other causes (refer to the differential diagnosis section of the consensus).

• Diagnostic criteria: including possible AEs and confirmed AEs:

⁃ Possible AEs: meet the three diagnostic criteria of A, B and D.

⁃ Confirmed AEs: meet the four diagnostic criteria of A, B, C and D. 1.1.5. AE symptoms occurred ≤9 months before randomization 1.1.6. Subjects meet new AEs

⁃ \- New onset: defined as subjects with NMDA-R or LGI-1 AEs and meeting the following criteria:

‣ The mRS score measured at baseline is stable (at least 24 hours) and is ≥2 points.

‣ Received the first acute first-line treatment within 6 weeks before randomization (baseline visit).

∙ 1.7. All females of childbearing potential and all males must use contraception during the study and for at least 30 days after the last dose of study treatment. In addition, subjects should not donate sperm or eggs during the study and for at least 30 days after the last dose of study treatment.

∙ 1.8. Stable neurological examination within 30 days before baseline (Visit 1).

∙ 2 Additional inclusion criteria for the NMDA-R AE cohort

⁃ In addition to the criteria outlined in Section 1.1, only subjects who met all of the following criteria were eligible for inclusion in the NMDA-R AE cohort:

‣ Age ≥ 18 years at the time of informed consent

‣ Informed consent, as appropriate based on patient age, specific site, and national criteria

‣ Suspected or definite NMDAR AE diagnosis as follows:

∙ 2.1. Suspected NMDAR encephalitis was diagnosed when all three of the following criteria were met: 1.2.1.1 Rapid onset (less than 3 months) of at least four of the following six cardinal symptoms:

‣ Abnormal (psychiatric) behavior or cognitive dysfunction

‣ Speech dysfunction (rushing speech, hypospeech, mutism)

‣ Seizures

‣ Ataxia, dyskinesia, or rigid/abnormal posture

‣ Decreased level of consciousness

‣ Autonomic dysfunction or central hypoventilation 1.2.1.2. At least one of the following laboratory results:

‣ Abnormal EEG (focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brushes)

‣ CSF with pleocytosis or oligoclonal bands 1.2.1.3. Reasonable exclusion of other etiologies and other clear encephalitis syndromes: for example, Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary angiitis of the central nervous system (CNS), Rasmussen encephalitis.

⁃ Note: If the above three groups of symptoms in criterion 1.2.1.1 are present and accompanied by systemic teratoma, suspected NMDAR encephalitis can also be diagnosed.

∙ 2.2 Definite NMDAR encephalitis can be diagnosed when the following three criteria are met at the same time: 1.2.2.1. The presence of one or more of the six main symptoms described in criterion 1.2.1.1 for suspected NMDAR encephalitis.

∙ 2.2.2. History of anti-NMDAR (GluN1) IgG antibodies detected in CSF using a cell-based assay.

∙ 2.3. Reasonable exclusion of other etiologies and other well-defined encephalitis syndromes: e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary angiitis of the central nervous system (CNS), Rasmussen encephalitis.

∙ 3 Other inclusion criteria for the LGI-1 AE cohort

⁃ In addition to the criteria outlined in Section 1.1, only subjects who meet all of the following criteria are eligible for inclusion in the LGI1 AE cohort:

∙ 3.1 Age ≥ 18 years at the time of signing the informed consent For subjects who are unable to provide informed consent due to the severity of their illness, the informed consent may be signed by their legally authorized representative at the time of obtaining the subject's consent, according to local requirements.

∙ 3.2 Diagnosis of LGI-1 AE

⁃ The diagnosis of LGI-1 encephalitis can be made when both of the following criteria are met:

∙ 3.2.1 Documented history of anti-LGI-1 IgG antibodies (in serum or CSF) using a cell-based assay.

∙ 3.2.2 Subacute onset (less than 4 months of development) of working memory deficits, seizures (including faciobrachial dystonic seizures), or psychiatric symptoms suggestive of limbic system involvement.

∙ 3.2.3 Diagnosis of LGI1 AE is reasonable when other etiologies and other well-defined encephalitis syndromes are excluded: e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary CNS vasculitis, Rasmussen encephalitis.

∙ 4 Other inclusion criteria for the AA AE cohort

⁃ In addition to the criteria outlined in Section 1.1, only subjects who meet all of the following criteria are eligible for inclusion in the AA AE cohort:

‣ Aged ≥ 18 years at the time of signing the informed consent form For subjects who are unable to provide informed consent due to the severity of their illness, the informed consent form may be signed by their legally authorized representative when the subject agrees, according to local requirements.

‣ Diagnosis of AA AE Meet the diagnosis of AE in 1.1, negative for anti-NMDA antibodies and anti-LGI-1 antibodies, and positive for at least one of the other anti-neuronal antibodies.

∙ 5 Inclusion criteria for viral encephalitis (hereinafter referred to as VE) cohort

⁃ The following four conditions must be met simultaneously for diagnosis of VE:

‣ Primary condition: altered mental status, including decreased level of consciousness, drowsiness, or abnormal mental behavior lasting ≥24 h; or new onset of epileptic seizure

‣ Secondary condition: fever ≥38 °C (before or within 72 h after onset), or new focal manifestations of the nervous system, or cerebrospinal fluid leukocytes ≥5×10\^6/L, or cerebrospinal fluid cytology showing lymphocytic inflammation, or imaging showing brain parenchymal lesions consistent with encephalitis, or abnormal electroencephalogram consistent with encephalitis

‣ Confirmatory laboratory test: positive cerebrospinal fluid viral nucleic acid (polymerase chain reaction or metagenomic next-generation sequencing), or positive cerebrospinal fluid and/or serum antiviral antibody IgM

‣ Reasonable exclusion of other causes

∙ 6 Healthy cohort:

‣ Age ≥ 18 years old when signing the informed consent form

‣ Healthy adult subjects without underlying diseases