Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
3.
J Neurol ; 267(7): 2101-2114, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32246252

ABSTRACT

OBJECTIVE: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. METHODS: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. RESULTS: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. CONCLUSIONS: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.


Subject(s)
Autoantibodies , Autoimmune Diseases of the Nervous System/diagnosis , Diagnostic Techniques, Neurological/standards , Glutamate Decarboxylase/immunology , Immunologic Tests/standards , Intracellular Signaling Peptides and Proteins/immunology , Membrane Proteins/immunology , Mental Disorders/diagnosis , Nerve Tissue Proteins/immunology , Neuropil/immunology , Potassium Channels, Voltage-Gated/immunology , Receptors, AMPA/immunology , Receptors, GABA-B/immunology , Receptors, Glycine/immunology , Receptors, N-Methyl-D-Aspartate/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Autoantibodies/analysis , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/blood , Autoimmune Diseases of the Nervous System/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/immunology , Child , Child, Preschool , Female , HEK293 Cells , Humans , Infant , Male , Mental Disorders/blood , Mental Disorders/cerebrospinal fluid , Mental Disorders/immunology , Middle Aged , Reproducibility of Results , Retrospective Studies , Young Adult
4.
J Neuroimmunol ; 189(1-2): 41-9, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17655939

ABSTRACT

Gene regulation in sepsis is known to be controlled by the transcription factor NF-kappaB. However, the function of neuronal NF-kappaB in sepsis is not well defined. In a mouse model of sepsis induced by i.p. injection of lipopolysaccharides (LPS), we found an activation of NF-kappaB in the brain as shown by the induction of a transgenic NF-kappaB reporter. Inhibition of neuronal NF-kappaB by cell-specific expression of the NF-kappaB super-repressor IkappaBalpha-SR improved LPS-induced hypothermia and survival but had no effect on body weight or on the humoral response to LPS. In contrast, glial inhibition of NF-kappaB did not influence body temperature and survival. By immunohistochemistry, we detected the active NF-kappaB subunit RelA in neuronal nuclei of the organum vasculosum of the lamina terminalis. Our data reveal an important role of neuronal NF-kappaB in thermoregulation and survival. The upcoming group of NF-kappaB inhibitors may have a place in the treatment of the acute-phase response.


Subject(s)
NF-kappa B/physiology , Neural Inhibition/physiology , Sepsis/mortality , Sepsis/physiopathology , Animals , Body Temperature/drug effects , Body Weight/drug effects , Brain/drug effects , Brain/pathology , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Embryo, Mammalian , Gene Expression Regulation/drug effects , Glial Fibrillary Acidic Protein/metabolism , Hypothermia/chemically induced , Hypothermia/physiopathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , NF-kappa B/genetics , Neural Inhibition/drug effects , Phosphopyruvate Hydratase/metabolism , Polysaccharides/adverse effects , Sepsis/chemically induced , Sepsis/pathology , Time Factors , Transfection
SELECTION OF CITATIONS
SEARCH DETAIL
...