Clinical significance of Kelch-like protein 11 antibodies

Objective: To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem cerebellar syndrome associated with testicular seminoma, and to determine the value of immunohistochemistry as a screen...

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Autores: Maudes, Estibaliz, Landa Medrano, Jon, Muñoz Lopetegi, Amaia, Armangué, Thaís, Alba, Mercedes, Saiz Hinarejos, Albert, Graus Ribas, Francesc, Dalmau Obrador, Josep, Sabater Baudet, Lidia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184091
Acceso en línea:https://hdl.handle.net/2445/184091
Access Level:acceso abierto
Palabra clave:Càncer de pulmó
Immunohistoquímica
Malalties del sistema nerviós central
Lung cancer
Immunohistochemistry
Central nervous system diseases
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spelling Clinical significance of Kelch-like protein 11 antibodiesMaudes, EstibalizLanda Medrano, JonMuñoz Lopetegi, AmaiaArmangué, ThaísAlba, MercedesSaiz Hinarejos, AlbertGraus Ribas, FrancescDalmau Obrador, JosepSabater Baudet, LidiaCàncer de pulmóImmunohistoquímicaMalalties del sistema nerviós centralLung cancerImmunohistochemistryCentral nervous system diseasesObjective: To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem cerebellar syndrome associated with testicular seminoma, and to determine the value of immunohistochemistry as a screening technique. Methods: Studies included 432 sera or CSF from 329 patients with paraneoplastic (157) or autoimmune neurologic syndromes (172); 63 with neurologic symptoms and benign teratomas; 28 with small-cell lung cancer, and 12 healthy subjects. KLHL11-abs were examined using a cell-based assay (CBA) with HEK293 cells transfected with a human KLHL11 clone. The CBA specificity was confirmed by immunoprecipitation. All positive samples were examined by immunohistochemistry on rat brain sections. Results: KLHL11-abs were detected in 32 patients by CBA, and patients' antibodies immunoprecipitated KLHL11. Using rat brain immunohistochemistry, only 7 samples (22%) were positive. Patients' median age was 28 years (range 9-76 years), and 16 (50%) were women. Tumors were identified in 23/32 (72%) patients, including 14 teratomas and 7 seminomas or mixed germ cell tumors. Thirteen (41%) patients had cerebellar ataxia (7) or encephalitis with brainstem cerebellar symptoms (6), 7 (22%) anti-NMDA receptor (NMDAR) encephalitis (5 with ovarian teratoma), 5 (16%) opsoclonus-myoclonus, 3 (9%) limbic encephalitis, and 4 (12%) diverse neurologic symptoms (3 with benign teratomas). Concurrent autoantibodies occurred in 14 (44%) patients (7 anti-NMDAR, 6 Ma2, and 1 Hu). Conclusions: KLHL11-abs associate with a spectrum of syndromes and tumors wider than those previously reported; 44% of patients have concurrent neuronal antibodies, some of them (anti-NMDAR) pathogenically relevant. Brain immunostaining is not useful for routine screening of KLHL11-abs.American Academy of Neurology2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/184091Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1212/NXI.000000000000066Neurology. Neuroimmunology & Neuroinflammation, 2020, vol. 7, num. 3, p. e666https://doi.org/10.1212/NXI.000000000000066cc-by-nc-nd (c) Maudes, Estíbaliz et al., 2020https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1840912026-05-27T06:46:51Z
dc.title.none.fl_str_mv Clinical significance of Kelch-like protein 11 antibodies
title Clinical significance of Kelch-like protein 11 antibodies
spellingShingle Clinical significance of Kelch-like protein 11 antibodies
Maudes, Estibaliz
Càncer de pulmó
Immunohistoquímica
Malalties del sistema nerviós central
Lung cancer
Immunohistochemistry
Central nervous system diseases
title_short Clinical significance of Kelch-like protein 11 antibodies
title_full Clinical significance of Kelch-like protein 11 antibodies
title_fullStr Clinical significance of Kelch-like protein 11 antibodies
title_full_unstemmed Clinical significance of Kelch-like protein 11 antibodies
title_sort Clinical significance of Kelch-like protein 11 antibodies
dc.creator.none.fl_str_mv Maudes, Estibaliz
Landa Medrano, Jon
Muñoz Lopetegi, Amaia
Armangué, Thaís
Alba, Mercedes
Saiz Hinarejos, Albert
Graus Ribas, Francesc
Dalmau Obrador, Josep
Sabater Baudet, Lidia
author Maudes, Estibaliz
author_facet Maudes, Estibaliz
Landa Medrano, Jon
Muñoz Lopetegi, Amaia
Armangué, Thaís
Alba, Mercedes
Saiz Hinarejos, Albert
Graus Ribas, Francesc
Dalmau Obrador, Josep
Sabater Baudet, Lidia
author_role author
author2 Landa Medrano, Jon
Muñoz Lopetegi, Amaia
Armangué, Thaís
Alba, Mercedes
Saiz Hinarejos, Albert
Graus Ribas, Francesc
Dalmau Obrador, Josep
Sabater Baudet, Lidia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pulmó
Immunohistoquímica
Malalties del sistema nerviós central
Lung cancer
Immunohistochemistry
Central nervous system diseases
topic Càncer de pulmó
Immunohistoquímica
Malalties del sistema nerviós central
Lung cancer
Immunohistochemistry
Central nervous system diseases
description Objective: To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem cerebellar syndrome associated with testicular seminoma, and to determine the value of immunohistochemistry as a screening technique. Methods: Studies included 432 sera or CSF from 329 patients with paraneoplastic (157) or autoimmune neurologic syndromes (172); 63 with neurologic symptoms and benign teratomas; 28 with small-cell lung cancer, and 12 healthy subjects. KLHL11-abs were examined using a cell-based assay (CBA) with HEK293 cells transfected with a human KLHL11 clone. The CBA specificity was confirmed by immunoprecipitation. All positive samples were examined by immunohistochemistry on rat brain sections. Results: KLHL11-abs were detected in 32 patients by CBA, and patients' antibodies immunoprecipitated KLHL11. Using rat brain immunohistochemistry, only 7 samples (22%) were positive. Patients' median age was 28 years (range 9-76 years), and 16 (50%) were women. Tumors were identified in 23/32 (72%) patients, including 14 teratomas and 7 seminomas or mixed germ cell tumors. Thirteen (41%) patients had cerebellar ataxia (7) or encephalitis with brainstem cerebellar symptoms (6), 7 (22%) anti-NMDA receptor (NMDAR) encephalitis (5 with ovarian teratoma), 5 (16%) opsoclonus-myoclonus, 3 (9%) limbic encephalitis, and 4 (12%) diverse neurologic symptoms (3 with benign teratomas). Concurrent autoantibodies occurred in 14 (44%) patients (7 anti-NMDAR, 6 Ma2, and 1 Hu). Conclusions: KLHL11-abs associate with a spectrum of syndromes and tumors wider than those previously reported; 44% of patients have concurrent neuronal antibodies, some of them (anti-NMDAR) pathogenically relevant. Brain immunostaining is not useful for routine screening of KLHL11-abs.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/184091
url https://hdl.handle.net/2445/184091
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1212/NXI.000000000000066
Neurology. Neuroimmunology & Neuroinflammation, 2020, vol. 7, num. 3, p. e666
https://doi.org/10.1212/NXI.000000000000066
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Maudes, Estíbaliz et al., 2020
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Maudes, Estíbaliz et al., 2020
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Academy of Neurology
publisher.none.fl_str_mv American Academy of Neurology
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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