Titre
Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Vogrig, A.
Auteure/Auteur
Péricart, S.
Auteure/Auteur
Pinto, A.L.
Auteure/Auteur
Rogemond, V.
Auteure/Auteur
Muñiz-Castrillo, S.
Auteure/Auteur
Picard, G.
Auteure/Auteur
Selton, M.
Auteure/Auteur
Mittelbronn, M.
Auteure/Auteur
Lanoiselée, H.M.
Auteure/Auteur
Michenet, P.
Auteure/Auteur
Benaiteau, M.
Auteure/Auteur
Pariente, J.
Auteure/Auteur
Zéphir, H.
Auteure/Auteur
Giordana, C.
Auteure/Auteur
Montaut, S.
Auteure/Auteur
Salhi, H.
Auteure/Auteur
Bachoumas, P.
Auteure/Auteur
Montcuquet, A.
Auteure/Auteur
Letovanec, I.
Auteure/Auteur
Uro-Coste, E.
Auteure/Auteur
Honnorat, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2632-1297
Statut éditorial
Publié
Date de publication
2021
Volume
3
Numéro
3
Première page
fcab185
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
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.
PID Serval
serval:BIB_2F9DBFA24660
PMID
Open Access
Oui
Date de création
2021-09-27T06:55:21.716Z
Date de création dans IRIS
2025-05-20T14:01:02Z
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Nom
34557666.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.33 MB
Format
Adobe PDF
PID Serval
serval:BIB_2F9DBFA24660.P001
URN
urn:nbn:ch:serval-BIB_2F9DBFA246603
Somme de contrôle
(MD5):9797b2c0de317ea24e0cfe8da477cd4d