HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
Gaig, Carles (Hospital Clínic i Provincial de Barcelona)
Ercilla, Guadalupe (Hospital Clínic i Provincial de Barcelona)
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ezquerra, Mario (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Fernández-Santiago, Rubén (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Palou, Eduard (Hospital Clínic i Provincial de Barcelona)
Sabater, Lidia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Höftberger, Romana (Medical University of Vienna)
Heidbreder, Anna (University Hospital Muenster (Alemanya))
Högl, Birgit (Medical University of Innsbruck)
Iranzo, Alex (Hospital Clínic i Provincial de Barcelona)
Santamaria Cano, Joan (Hospital Clínic i Provincial de Barcelona)
Dalmau, Josep (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Graus Ribas, Francesc (Institut d'Investigacions Biomèdiques August Pi i Sunyer)

Data:	2019
Resum:	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.
Ajuts:	Instituto de Salud Carlos III FIS 15/00377 Instituto de Salud Carlos III FIS 14/00203 Instituto de Salud Carlos III FIS 18/00067 Ministerio de Economía y Competitividad SAF2015-73508-JIN
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Autoimmune diseases ; Association studies in genetics
Publicat a:	Neurology® neuroimmunology & neuroinflammation, Vol. 6, issue 6 (Nov. 2019) , ISSN 2332-7812

DOI: 10.1212/NXI.0000000000000605
PMID: 31454761

11 p, 247.4 KB

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