PT  - JOURNAL ARTICLE
AU  - Carles Gaig
AU  - Guadalupe Ercilla
AU  - Xavier Daura
AU  - Mario Ezquerra
AU  - Ruben Fernández-Santiago
AU  - Eduard Palou
AU  - Lidia Sabater
AU  - Romana Höftberger
AU  - Anna Heidbreder
AU  - Birgit Högl
AU  - Alex Iranzo
AU  - Joan Santamaria
AU  - Josep Dalmau
AU  - Francesc Graus
TI  - HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
AID  - 10.1212/NXI.0000000000000605
DP  - 2019 Nov 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e605
VI  - 6
IP  - 6
4099  - http://nn.neurology.org/content/6/6/e605.short
4100  - http://nn.neurology.org/content/6/6/e605.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Nov 01; 6
AB  - Objectives 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.Methods 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.Results 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).Conclusions 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.CBD=corticobasal degeneration; MAPT=microtubule-associated protein tau; PSP=progressive supranuclear palsy