T cells in patients with narcolepsy target self-antigens of hypocretin neurons

Latorre, Daniela; Kallweit, Ulf; Armentani, Eric; Foglierini, Mathilde; Mele, Federico; Cassotta, Antonino; Jovic, Sandra; Jarrossay, David; Mathis, Johannes; Zellini, Francesco; Becher, Burkhard; Lanzavecchia, Antonio; Khatami, Ramin; Manconi, Mauro; Tafti, Mehdi; Bassetti, Claudio; Sallusto, Federica

doi:10.1038/s41586-018-0540-1

Cited by 281 publications

(235 citation statements)

References 38 publications

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“…Latorre et al . showed sharing of hypocretin‐specific T‐cell clones between patients suffering from narcolepsy. In some patients, self‐reactive clonotypes were among the most frequent in peripheral blood, suggesting intense clonal expansion.…”

Section: Clonal Sharingmentioning

confidence: 99%

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

2019

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Summary B‐cell receptors and T‐cell receptors are the key molecules responsible for specific antigen recognition in adaptive immunity. The huge diversity of immune receptor repertoires constrained their comprehensive studies in the past. More recently, however, high‐throughput sequencing based techniques have revolutionized the field of immune receptor repertoire profiling enabling new insights into the development and function of the adaptive immune system. In this review we describe current methods for immune receptor profiling and software tools used for repertoire reconstruction from raw sequencing data. We also provide examples of how immune repertoire profiling can be used to study adaptive immunity in disease and in the course of organ and bone marrow transplantation.

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Section: Clonal Sharingmentioning

confidence: 99%

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

2019

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“…Sequence analysis of rearranged TCR Vβ genes of NZM-specific T cell clones was performed as previously described 31 . Briefly, cDNA from individual T cell clones was obtained by reverse transcription of total RNA from 10 3 -10 4 cells per reaction.…”

Section: Sequence Analysis Of Tcr Vβ Genesmentioning

confidence: 99%

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Cassotta

Mikol

Bertrand

et al. 2019

Nat Med

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“…12,13 Direct proof of an autoimmune aetiology and pathogenesis of NT1 has been lacking as no studies have been able to demonstrate an immune-mediated pathogenesis against the hypocretin neurons. Autoreactive T cells towards hypocretin peptides were recently reported, [14][15][16] and additional studies are therefore warranted to dissect the possible autoimmunity in NT1.…”

Section: Introductionmentioning

confidence: 99%

Screening for autoantibody targets in post‐vaccination narcolepsy using proteome arrays

et al. 2020

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Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin‐producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®‐vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two‐step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®‐vaccination. Using arrays of more than 9000 full‐length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first‐degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α‐MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®‐induced NT1.

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T cells in patients with narcolepsy target self-antigens of hypocretin neurons

Cited by 281 publications

References 38 publications

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Screening for autoantibody targets in post‐vaccination narcolepsy using proteome arrays

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