Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study

Abstract

BackgroundAntibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab.Case presentationWe report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR+ CD8+ T-lymphocytes (fCD8+TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8+TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8+TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described.ConclusionThe correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.

Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy

“…Some cases might demonstrate known or newer ABs in the course of their disease . In addition, and parallel to an ongoing study in GAD65 AB‐positive LE, Flow‐Cytometric analysis of, for example, liquor lymphocyte configuration could help to verify whether the observed indirect signs of a suggested autoimmune encephalitis can be confirmed or not .…”

CD8+ T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing

“…The second patient with corresponding CSF–peripheral blood samples (RE patient #20) was experimentally treated off-label with basiliximab, a monoclonal antibody directed against the interleukin-2 receptor alpha chain CD25 (ref. 22 ). While this drug is usually reserved for patients with renal transplants, the blockade of CD25, which is expressed on activated T cells, was hypothesized to dampen the inflammatory immune response in this RE case.…”

Stereotactically Injected Kv1.2 and CASPR2 Antisera Cause Differential Effects on CA1 Synaptic and Cellular Excitability, but Both Enhance the Vulnerability to Pro-epileptic Conditions

“…Nonetheless, Kv1.1 and Kv1.2 are predominant target structures of autoimmune pathology in LE and Morvan syndrome (Kleopa et al, 2006). Hence, our studies can help distinguish clinically relevant autoantibodies from those representing rather as an epiphenomenon such as anti-GAD65 (Stemmler et al, 2015;Widman et al, 2015;Hackert et al, 2016). Moreover, the present study showed that anti-Kv1.2 and anti-CASPR2 differed in their cellular effects, but both led to hyperexcitability.…”