HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease

We investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic fi...

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Autores: Gaig, Carles|||0000-0002-7113-8125, Ercilla, Guadalupe, Daura i Ribera, Xavier|||0000-0001-9235-6730, Ezquerra, Mario|||0000-0003-3246-6641, Fernández-Santiago, Rubén|||0000-0002-4582-0702, Palou, Eduard|||0000-0003-1544-1485, Sabater, Lidia, Höftberger, Romana|||0000-0002-5769-1100, Heidbreder, Anna, Högl, Birgit, Iranzo, Alex|||0000-0002-5618-8271, Santamaria Cano, Joan|||0000-0003-0879-4135, Dalmau, Josep|||0000-0001-5856-2813, Graus Ribas, Francesc|||0000-0002-8924-8322
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:226593
Acceso en línea:https://ddd.uab.cat/record/226593
https://dx.doi.org/urn:doi:10.1212/NXI.0000000000000605
Access Level:acceso abierto
Palabra clave:Autoimmune diseases
Association studies in genetics
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spelling HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 diseaseGaig, Carles|||0000-0002-7113-8125Ercilla, GuadalupeDaura i Ribera, Xavier|||0000-0001-9235-6730Ezquerra, Mario|||0000-0003-3246-6641Fernández-Santiago, Rubén|||0000-0002-4582-0702Palou, Eduard|||0000-0003-1544-1485Sabater, LidiaHöftberger, Romana|||0000-0002-5769-1100Heidbreder, AnnaHögl, BirgitIranzo, Alex|||0000-0002-5618-8271Santamaria Cano, Joan|||0000-0003-0879-4135Dalmau, Josep|||0000-0001-5856-2813Graus Ribas, Francesc|||0000-0002-8924-8322Autoimmune diseasesAssociation studies in geneticsWe investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic findings of a novel neuronal-specific tauopathy. We compared the HLA alleles and MAPT H1/H1 genotype of 35 patients with anti-IgLON5 with healthy controls. The on-line server tool NetMHCIIpan 3.1 was used to predict the IgLON5 peptide binding to HLA Class II molecules. The HLA-DRB1*10:01-DQB1*05:01 haplotype was overrepresented in patients with anti-IgLON5 disease (OR = 54.5; 95% CI: 22.2-133.9, p < 0.0001). In addition, HLA-DQA was genotyped in 27 patients, and 25 (92.6%) of them had DQ molecules composed by DQA1*01 and DQB1*05 chains compared with 148/542 (27.3%) controls (OR = 43.9; 95% CI: 10.4-185.5, p < 0.0001). Patients DRB1*10:01 positive developed more frequently sleep or bulbar symptoms than those carrying other HLA alleles (70.0% vs 26.7%; p = 0.011). Prediction algorithms identified 2 IgLON5 peptides (1 located in the signal sequence) that showed strong binding to HLA-DRB1*10:01 and other HLA-DRB1, but not to HLA-DQA and HLA-DQB molecules. The MAPT H1/H1 homozygous genotype was present in 20/24 (83.3%) anti-IgLON5 Caucasian patients compared with 54/116 (46.5%) healthy controls (p = 0.0007). The robust association of anti-IgLON5 disease with distinct HLA Class II molecules supports a primary autoimmune origin. The significant association of MAPT H1 haplotype also suggests that an underlying neurodegenerative process could be involved in anti-IgLON5 disease. 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226593https://dx.doi.org/urn:doi:10.1212/NXI.0000000000000605reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS15/00377Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS14/00203Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS18/00067Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-73508-JINopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2265932026-06-06T12:50:31Z
dc.title.none.fl_str_mv HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
title HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
spellingShingle HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
Gaig, Carles|||0000-0002-7113-8125
Autoimmune diseases
Association studies in genetics
title_short HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
title_full HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
title_fullStr HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
title_full_unstemmed HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
title_sort HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
dc.creator.none.fl_str_mv Gaig, Carles|||0000-0002-7113-8125
Ercilla, Guadalupe
Daura i Ribera, Xavier|||0000-0001-9235-6730
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Palou, Eduard|||0000-0003-1544-1485
Sabater, Lidia
Höftberger, Romana|||0000-0002-5769-1100
Heidbreder, Anna
Högl, Birgit
Iranzo, Alex|||0000-0002-5618-8271
Santamaria Cano, Joan|||0000-0003-0879-4135
Dalmau, Josep|||0000-0001-5856-2813
Graus Ribas, Francesc|||0000-0002-8924-8322
author Gaig, Carles|||0000-0002-7113-8125
author_facet Gaig, Carles|||0000-0002-7113-8125
Ercilla, Guadalupe
Daura i Ribera, Xavier|||0000-0001-9235-6730
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Palou, Eduard|||0000-0003-1544-1485
Sabater, Lidia
Höftberger, Romana|||0000-0002-5769-1100
Heidbreder, Anna
Högl, Birgit
Iranzo, Alex|||0000-0002-5618-8271
Santamaria Cano, Joan|||0000-0003-0879-4135
Dalmau, Josep|||0000-0001-5856-2813
Graus Ribas, Francesc|||0000-0002-8924-8322
author_role author
author2 Ercilla, Guadalupe
Daura i Ribera, Xavier|||0000-0001-9235-6730
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Palou, Eduard|||0000-0003-1544-1485
Sabater, Lidia
Höftberger, Romana|||0000-0002-5769-1100
Heidbreder, Anna
Högl, Birgit
Iranzo, Alex|||0000-0002-5618-8271
Santamaria Cano, Joan|||0000-0003-0879-4135
Dalmau, Josep|||0000-0001-5856-2813
Graus Ribas, Francesc|||0000-0002-8924-8322
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autoimmune diseases
Association studies in genetics
topic Autoimmune diseases
Association studies in genetics
description We investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic findings of a novel neuronal-specific tauopathy. We compared the HLA alleles and MAPT H1/H1 genotype of 35 patients with anti-IgLON5 with healthy controls. The on-line server tool NetMHCIIpan 3.1 was used to predict the IgLON5 peptide binding to HLA Class II molecules. The HLA-DRB1*10:01-DQB1*05:01 haplotype was overrepresented in patients with anti-IgLON5 disease (OR = 54.5; 95% CI: 22.2-133.9, p < 0.0001). In addition, HLA-DQA was genotyped in 27 patients, and 25 (92.6%) of them had DQ molecules composed by DQA1*01 and DQB1*05 chains compared with 148/542 (27.3%) controls (OR = 43.9; 95% CI: 10.4-185.5, p < 0.0001). Patients DRB1*10:01 positive developed more frequently sleep or bulbar symptoms than those carrying other HLA alleles (70.0% vs 26.7%; p = 0.011). Prediction algorithms identified 2 IgLON5 peptides (1 located in the signal sequence) that showed strong binding to HLA-DRB1*10:01 and other HLA-DRB1, but not to HLA-DQA and HLA-DQB molecules. The MAPT H1/H1 homozygous genotype was present in 20/24 (83.3%) anti-IgLON5 Caucasian patients compared with 54/116 (46.5%) healthy controls (p = 0.0007). The robust association of anti-IgLON5 disease with distinct HLA Class II molecules supports a primary autoimmune origin. The significant association of MAPT H1 haplotype also suggests that an underlying neurodegenerative process could be involved in anti-IgLON5 disease.
publishDate 2019
dc.date.none.fl_str_mv 2
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/226593
https://dx.doi.org/urn:doi:10.1212/NXI.0000000000000605
url https://ddd.uab.cat/record/226593
https://dx.doi.org/urn:doi:10.1212/NXI.0000000000000605
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS15/00377
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS14/00203
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS18/00067
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-73508-JIN
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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