RT Journal Article
SR Electronic
T1 HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e605
DO 10.1212/NXI.0000000000000605
VO 6
IS 6
A1 Carles Gaig
A1 Guadalupe Ercilla
A1 Xavier Daura
A1 Mario Ezquerra
A1 Ruben Fernández-Santiago
A1 Eduard Palou
A1 Lidia Sabater
A1 Romana Höftberger
A1 Anna Heidbreder
A1 Birgit Högl
A1 Alex Iranzo
A1 Joan Santamaria
A1 Josep Dalmau
A1 Francesc Graus
YR 2019
UL http://nn.neurology.org/content/6/6/e605.abstract
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