Individualized therapy guided by single-cell sequencing in anti-GABAR encephalitis.

We presented a patient with refractory anti-GABA-R encephalitis, and constructed libraries for single-cell sequencing from the patient's peripheral blood mononuclear cells (PBMCs), cerebrospinal fluid cells, as well as four healthy volunteer's PBMCs. A distinct group of monoclonal CD8 T cells and an abnormal JAK-STAT signaling pathway was implicated in the disease. The cross-reactive protein LIM-domain-only protein 5 (LMO5) identified in the patient's thymoma, prompted the activation of the specific CD8 T cells.

A Comparative Study of 141 Glial Fibrillary Acidic Protein Immunoglobulin G Positive Cases.

Background: Glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG) positivity is associated with autoimmune GFAP astrocytopathy (GFAP-A), but also with other autoimmune encephalitides and viral infections. We attempted to elucidate the characteristics of GFAP-A in relation to other GFAP-IgG-positive encephalitides and constructed a differential diagnosis model.

Methods: 141 GFAP-IgG-positive cases were identified, including 52 astrocytopathy (GFAP-A group), 48 autoimmune encephalitis (AE-G), and 41 viral encephalitis (VE-G).

Immunoregulatory programs in anti-N-methyl-D-aspartate receptor encephalitis identified by single-cell multi-omics analysis.

Background: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a prevalent type of autoimmune encephalitis caused by antibodies targeting the NMDAR's GluN1 subunit. While significant progress has been made in elucidating the pathophysiology of autoimmune diseases, the immunological mechanisms underlying anti-NMDARE remain elusive. This study aimed to characterize immune cell interactions and dysregulation in anti-NMDARE by leveraging single-cell multi-omics sequencing technologies.

Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases.

Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.

Cerebrospinal fluid uric acid levels associated with disease severity in patients with anti-N-methyl-d-aspartate receptor encephalitis.

Introduction: Uric acid (UA) is an important natural antioxidant and strong peroxynitrite scavenger, but little is known about central nervous system (CNS) levels of UA in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDARE).

Methods: Cerebrospinal fluid (CSF) and serum levels of UA were determined in 72 patients with anti-NMDARE and 111 controls with non-inflammatory neurological diseases (NINDs). Serum UA levels were also evaluated in 132 healthy controls (HCs).

CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.

Chitinase-3-like protein 1 (CHI3L1) is primarily secreted by activated astrocytes in the brain and is known as a reliable biomarker for inflammatory central nervous system (CNS) conditions such as neurodegeneration and autoimmune disorders like neuromyelitis optica (NMO). NMO is an astrocyte disease caused by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4) and leads to vision loss, motor deficits, and cognitive decline. In this study examining CHI3L1's biological function in neuroinflammation, we found that CHI3L1 expression correlates with cognitive impairment in our NMO patient cohort.

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

Unlabelled: To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses.

Methods: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs).

CD8 T-cell predominance in autoimmune glial fibrillary acidic protein astrocytopathy.

Background And Objective: We aimed to report the pathological features of T lymphocytes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A).

Methods: A retrospective pathological analysis of patients with GFAP-A was performed.

Results: Eight patients with GFAP-immunoglobulin G (IgG) and pathological data were included.

Autoimmune glial fibrillary acidic protein astrocytopathy mimics infectious meningitis: Two case reports.

Background: Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) has been recently characterized as a novel autoimmune central nervous system (CNS) disorder with GFAP antibody as the biomarker. However, nonspecific symptoms of A-GFAP-A contribute to misdiagnosis.

Case Presentation: The patients presented with initial symptoms of fever, headache, and nuchal rigidity.

Clinical Heterogeneity in Patients with Glutamate Decarboxylase Antibody.

Objective: To explore the diversity and clinical features of anti-glutamate decarboxylase (GAD) antibody-associated neurological diseases.

Methods: Clinical data of a series of 5 patients positive for anti-GAD antibodies were retrospectively analyzed.

Results: All 5 patients were female, with a median age of 41.

Silencing the NR2B gene in rat ACC neurons by lentivirus-delivered shRNA alleviates pain-related aversion.

The N-methyl-D-aspartate (NMDA) receptor NR2B subunit on neurons in the anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli. Selectively silencing this NR2B subunit in ACC neurons could therefore alleviate pain-related aversion. However, to date, there is no optimal approach to selectively silence the NR2B gene in ACC neurons.