Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis.
Brain Commun
; 3(3): fcab185, 2021.
Article
em En
| MEDLINE
| ID: mdl-34557666
ABSTRACT
In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis (n = 105), cerebellar degeneration (n = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis (n = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma (n = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice. Overall, Kelch-like protein 11 antibodies were detected in 11 patients [11/11, 100% were male; their median (range) age was 44 (35-79) years], 9 of them from the antibody-negative paraneoplastic neurological syndrome cohort, 1 from the antibody-positive (Ma2-Ab) cohort and 1 additional prospectively detected patient. All patients manifested a cerebellar syndrome, either isolated (4/11, 36%) or part of a multi-system neurological disorder (7/11, 64%). Additional core syndromes were limbic encephalitis (5/11, 45%) and myelitis (2/11, 18%). Severe weight loss (7/11, 64%) and hearing loss/tinnitus (5/11, 45%) were common. Rarer neurologic manifestations included hypersomnia and seizures (2/11, 18%). Two patients presented phenotypes resembling primary neurodegenerative disorders (progressive supranuclear palsy and flail arm syndrome, respectively). An associated cancer was found in 9/11 (82%) patients; it was most commonly (7/9, 78%) a spontaneously regressed ('burned-out') testicular germ cell tumour. A newly designed clinical score (MATCH score male, ataxia, testicular cancer, hearing alterations) with a cut-off ≥4 successfully identified patients with Kelch-like protein 11 antibodies (sensitivity 78%, specificity 99%). Pathological findings (three testicular tumours, three lymph node metastases of testicular tumours, one brain biopsy) showed the presence of a T-cell inflammation with resulting anti-tumour immunity in the testis and one chronic, exhausted immune response-demonstrated by immune checkpoint expression-in the metastases and the brain. In conclusion, these findings suggest that Kelch-like protein 11 antibody paraneoplastic neurological syndrome is a homogeneous clinical syndrome and its detection can be facilitated using the MATCH score. The pathogenesis is probably T-cell mediated, but the stages of inflammation are different in the testis, metastases and the brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Brain Commun
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM