Pubblicazioni

Autori:

Yogeshwar, Selina M; Muñiz-Castrillo, Sergio; Sabater, Lidia; Peris-Sempere, Vicente; Mallajosyula, Vamsee; Luo, Guo; Yan, Han; Yu, Eric; Zhang, Jing; Lin, Ling; Fagundes Bueno, Flavia; Ji, Xuhuai; Picard, Géraldine; Rogemond, Véronique; Pinto, Anne Laurie; Heidbreder, Anna; Höftberger, Romana; Graus, Francesc; Dalmau, Josep; Santamaria, Joan; Iranzo, Alex; Schreiner, Bettina; Giannoccaro, Maria Pia; Liguori, Rocco; Shimohata, Takayoshi; Kimura, Akio; Ono, Yoya; Binks, Sophie; Mariotto, Sara; Dinoto, Alessandro; Bonello, Michael; Hartmann, Christian J; Tambasco, Nicola; Nigro, Pasquale; Prüss, Harald; Mckeon, Andrew; Davis, Mark M; Irani, Sarosh R; Honnorat, Jérôme; Gaig, Carles; Finke, Carsten; Mignot, Emmanuel

Titolo:

HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

A Stampa

Referee:

Sì

Nome rivista:

Brain

ISSN Rivista:

0006-8950

N° Volume:

147

Numero o Fascicolo:

7

Intervallo pagine:

2579-2592

Parole chiave:

HLA; IgLON5; T cell; autoimmune encephalitis; autoimmunity

Breve descrizione dei contenuti:

Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement, and bulbar-associated dysfunction. Presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, support an autoimmune basis. In this study, a multicentric HLA study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared to one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease.

Pagina Web:

https://doi.org/10.1093/brain/awae048

Id prodotto:

138287

Handle IRIS:

11562/1121088

ultima modifica:

22 settembre 2024

Citazione bibliografica:

Yogeshwar, Selina M; Muñiz-Castrillo, Sergio; Sabater, Lidia; Peris-Sempere, Vicente; Mallajosyula, Vamsee; Luo, Guo; Yan, Han; Yu, Eric; Zhang, Jing; Lin, Ling; Fagundes Bueno, Flavia; Ji, Xuhuai; Picard, Géraldine; Rogemond, Véronique; Pinto, Anne Laurie; Heidbreder, Anna; Höftberger, Romana; Graus, Francesc; Dalmau, Josep; Santamaria, Joan; Iranzo, Alex; Schreiner, Bettina; Giannoccaro, Maria Pia; Liguori, Rocco; Shimohata, Takayoshi; Kimura, Akio; Ono, Yoya; Binks, Sophie; Mariotto, Sara; Dinoto, Alessandro; Bonello, Michael; Hartmann, Christian J; Tambasco, Nicola; Nigro, Pasquale; Prüss, Harald; Mckeon, Andrew; Davis, Mark M; Irani, Sarosh R; Honnorat, Jérôme; Gaig, Carles; Finke, Carsten; Mignot, Emmanuel, HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease «Brain» , vol. 147 , n. 7 , 2024 , pp. 2579-2592

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