Evidence of a pathogenic role for CD8
            <sup>+</sup>
            T cells in anti-GABA
            <sub>B</sub>
            receptor limbic encephalitis

Golombeck, Kristin S.; Bönte, Kathrin; Mönig, Constanze; Loo, Karen M. van; Hartwig, Marvin; Schwindt, Wolfram; Widman, Guido; Lindenau, Matthias; Becker, Albert; Glatzel, Markus; Elger, Christian E.; Wiendl, Heinz; Meuth, Sven G.; Lohmann, Hubertus; Groß, Catharina C.; Melzer, Nico

doi:10.1212/nxi.0000000000000232

Cited by 51 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 In autoimmune encephalitis, much attention has been paid to analyses of antibodies, whereas T cell responses have rarely been studied. [21][22][23][24] We here found parallel intrathecal and parenchymal expansions of a likely pathogenic CD8+ T cell clone supporting the assumption that T cells have so far been unjustifiably disregarded. The link between the dominant role of autoantibodies and concomitant invasion of putatively pathogenic T cell clones requires further investigation in order to reveal the synergy between both arms of the adaptive immune system.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis

Bracher

Alcalá

Ferrer

et al. 2020

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

The role of T cells in autoimmune encephalitis syndromes with autoantibodies against cell surface antigens is still enigmatic. Here we analyzed the T cell receptor repertoires of CD8+ and CD4+ T cells in a patient with “idiopathic” gamma‐aminobutyric‐acid‐A receptor (GABAA‐R) encephalitis by next‐generation sequencing and single‐cell analyses. We identified a CD8+ T cell clone that was strongly expanded in the cerebrospinal fluid and in the hippocampus but not in the operculo‐insular cortex. By contrast, CD4+ T cells were polyclonal in these tissues. Such a strong clonal expansion suggests that CD8+ T cells may play a significant role in the pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 80%

“…In autoimmune encephalitis, much attention has been paid to analyses of antibodies, whereas T cell responses have rarely been studied . We here found parallel intrathecal and parenchymal expansions of a likely pathogenic CD8+ T cell clone supporting the assumption that T cells have so far been unjustifiably disregarded.…”

Section: Discussionsupporting

confidence: 74%

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis

Bracher

Alcalá

Ferrer

et al. 2020

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is a major finding of the present study that the quantitative RT-PCR data not only confirmed the delayed T-cell response, but was also able to demonstrate that the increase was attributable to an enhanced CD8 + T-cell population. While the pathophysiological role of CD8 + cells has already been suggested in the rodent kainate model [ 34 ], there is recent evidence on the pathogenic role of CD8 + cells in autoimmune anti-GABA-B-receptor encephalitis in humans [ 36 ], but intriguingly, also human temporal lobe epilepsy [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

et al. 2017

View full text Add to dashboard Cite

Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4–5 weeks old C57BL/6 mice. Brains were removed at days 1–4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0–3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention.

show abstract

“…Likewise, there were no reports of investigations undertaken to explain the relationship between anti-GABA B -R encephalitis and AE with AS. Some research has suggested that T cell-based autoimmunity plays an important role in the development of anti-GABA B -R encephalitis [ 4 ]. Similarly, T cells were found to act in key pathogenetic roles in AS, as well [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

A case of anti-gamma-aminobutyric acid-B receptor encephalitis coexisting with ankylosing spondylitis

Wang

Lin

et al. 2020

Neurol Sci

View full text Add to dashboard Cite

Dear Editor, Anti-gamma-aminobutyric acid-B receptor (GABA B-R) encephalitis, autoimmune encephalitis (AE) associated with anti-neuronal cell surface antibodies, presents with prominent seizures, behavioral changes, and cognitive deficits. Half of the cases of anti-GABA B-R encephalitis have been associated with tumors, especially small-cell lung cancer [1]. Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory condition affecting the spine and sacroiliac joint [2], which leads to back pain and progressive spinal stiffness. However, the co-occurrence of anti-GABA B-R encephalitis and AS has never been reported. Here, we provide a case report of anti-GABA B-R encephalitis coexisting with AS for the first time. A Chinese man, whose HLA-B27 and anti-GABA B-R antibodies were positive, was diagnosed with anti-GABA B-R encephalitis and AS. A 34-year-old man presented with his first generalized tonic-clonic seizure (GTCS) lasting for 1 min, 20 days before this admission. After a neurological evaluation and head computed tomography (CT) scan in the emergency department, he was prescribed sodium valproate 500 mg twice daily. However, he experienced another GTCS which lasted for 3 min, 20 days after his first GTCS. Other symptoms included psychiatric abnormalities, such as irritability, delirium, and behavioral changes, in addition to more frequent seizure attacks observed on the following days. The patient experienced GTCSs one-to-four times daily with each episode lasting for 1-3 min. He reported a history of lower back pain and fatigue for 2 years without any evaluation or treatment. An aunt of the patient had a history of ankylosing spondylitis. Neurological examination showed a decline in cognitive function, which mainly affected short-term memory, and disorientation in time and space was revealed. The results of cranial nerve (the first cranial nerve was not tested), motor system, tendon reflexes, meningeal irritation sign, and Babinski sign examinations were generally normal. It was not possible to completely examine the patient's sensory system or motor coordination. GABA B-R antibodies were found in the serum (1:10) and cerebrospinal fluid (CSF) (1:10) using a Cytometric Bead Array (Fig. 1) (Euroimmun, Lubeck, Germany). Serum and CSF were both negative for antibodies against neuronal surface antigens, including antibodies to N-methyl-D-aspartate (NMDA) receptors, leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor (AMPAR), dipeptidylpeptidase-like protein-6 (DPPX), and metabotropic glutamate receptor 5 (mGluR5). Tests for paraneoplastic antibodies (anti-Hu, anti-Yo, anti-Ri, anti-GAD, anti-PCA2, anti-Ma2/Ta, anti-CV2/CRMP5, anti-ANNA-3, and antiamphiphysin) in serum and CSF were negative. Antivoltage-gated calcium channel (VGCC) antibodies (using radioimmunoprecipitation) were negative in serum, as Aiqing Li and Weihua Feng contributed equally to this work.

show abstract

Evidence of a pathogenic role for CD8 ⁺ T cells in anti-GABA _B receptor limbic encephalitis

Cited by 51 publications

References 33 publications

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

A case of anti-gamma-aminobutyric acid-B receptor encephalitis coexisting with ankylosing spondylitis

Contact Info

Product

Resources

About

Evidence of a pathogenic role for CD8 + T cells in anti-GABA B receptor limbic encephalitis

Cited by 51 publications

References 33 publications

An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis

An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

A case of anti-gamma-aminobutyric acid-B receptor encephalitis coexisting with ankylosing spondylitis

Contact Info

Product

Resources

About

Evidence of a pathogenic role for CD8 ⁺ T cells in anti-GABA _B receptor limbic encephalitis

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis

An expanded parenchymal CD8+ T cell clone in GABA_A receptor encephalitis