0000000000164078

AUTHOR

Klaus Dornmair

showing 3 related works from this author

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis

2008

T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue. We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog−/−), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neur…

Encephalomyelitis Autoimmune ExperimentalMultiple SclerosisT-LymphocytesMolecular Sequence DataReceptors Antigen T-CellMice TransgenicCross ReactionsMajor histocompatibility complexAutoantigensGeneral Biochemistry Genetics and Molecular BiologyEpitopeMyelin oligodendrocyte glycoproteinMice03 medical and health sciencesMyelin0302 clinical medicineAntigenNeurofilament ProteinsAnimalsMedicineAmino Acid SequenceMyelin Sheath030304 developmental biologyAutoimmune disease0303 health sciencesbiologybusiness.industryExperimental autoimmune encephalomyelitisT-cell receptorGeneral Medicinemedicine.disease3. Good healthMice Inbred C57BLDisease Models AnimalMyelin-Associated Glycoproteinmedicine.anatomical_structureImmunologybiology.proteinMyelin-Oligodendrocyte GlycoproteinbusinessMyelin Proteins030215 immunologyNature Medicine
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Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA(A) receptor encephalitis

2021

Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA A -R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABA A -R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABA A -R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to…

AutoimmunityCross Reactionsmedicine.disease_causeCross-reactivityAutoantigensPathogenesisAutoimmune Diseases of the Nervous SystemAntigens NeoplasmmedicineHumansAutoantibodiesAutoimmune encephalitisB-LymphocytesMultidisciplinarybiologyPyramidal CellsAutoantibodyGABA-A-receptor encephalitis autoantibody autoimmune encephalitis epilepsy paraneoplastic encephalitisBiological Sciencesmedicine.diseaseReceptors GABA-ATumor antigennervous systemImmunologybiology.proteinImmunohistochemistryEncephalitisDisease SusceptibilityAntibodyEncephalitisBiomarkers
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Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation

2014

Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ∼40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied …

AdultMaleMultiple SclerosisMolecular Sequence DataSomatic hypermutationAntibodies Monoclonal HumanizedImmunoglobulin GAffinity maturationYoung AdultmedicineHumansAmino Acid SequenceAgedCell ProliferationAged 80 and overInflammationB-LymphocytesBase SequencebiologyNatalizumabMultiple sclerosisGerminal centerCytidine deaminaseMiddle Agedmedicine.diseaseImmunoglobulin MSpinal CordImmunoglobulin class switchingImmunoglobulin MImmunoglobulin GImmunologybiology.proteinFemaleSomatic Hypermutation ImmunoglobulinNeurology (clinical)Single-Cell AnalysisBrain
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