6533b853fe1ef96bd12ac2e1
RESEARCH PRODUCT
Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA(A) receptor encephalitis
Alexander M. HerrmannCarmen AlcaláSven G. MeuthStefan BittnerSimone M. BrändleNico MelzerFrank LeypoldtAmélie F MenkeDavid GebertLisa Ann GerdesKlaus DornmairBonaventura CasanovaBianca TeegenTania KümpfelHannah L. PellkoferLars KomorowskiReinhard HohlfeldKathrin HeldManuela CerinaEduardo BeltránSusanne Webersubject
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 SusceptibilityAntibodyEncephalitisBiomarkersdescription
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 clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABA A -R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABA A -R and LMO5 is frequent in GABA A -R encephalitis and supports the hypothesis of a paraneoplastic etiology.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-02-22 |