mRNA and T cell receptor sequencing of patients with Pandemrix-associated narcolepsy type 1

Increased risk of Narcolepsy type 1 (NT1) was reported among children and adolescents vaccinated with AS03-adjuvanted pandemic influenza A vaccine (H1N1; Pandemrix®). We hypothesized that viral T cell epitope(s) in Pandemrix mimicked self-epitope(s), and that recognition of these cross-reactive epitopes contributed to disease-specific autoimmunity. We demonstrate that pediatric, Pandemrix-associated NT1 patients had enhanced T-cell immunity against dominant T-cell epitopes of Pandemrix vaccine viral proteins neuraminidase (NA) and nucleoprotein (NP), and also responded against a self-epitope in brain-expressed protein-O-mannosyltransferase 1 (POMT1). Here, the gene expression profiles and TCR repertoire of PBMC from patients and healthy controls were compared. PBMC samples were stimulated with peptides NA-175-189 or POMT1-675-589, and bulk RNA isolated and sequenced (RNAseq and TCRseq).

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001006796	PBMCs isolated from 27 individuals (11 narcolepsy type 1 patients, 16 healthy controls) were stimulated with the peptide Neuroaminidase 175-189 or Protein-O-mannosyl transferase 1 (POMT1) 675-689 or media as control. FACS sorted CD4+ and CD8+ lymphocytes from one patient were subjected to the same stimulation. Transcriptome profiling was done with a 3' tagging protocol. T cell receptor repertoires were profiled with amplicon sequencing (Rep-seq). The dataset contains FASTQ files with sequencing reads, transcript count matrices and TCR clonotypes.	Illumina MiSeq NextSeq 500	82
EGAD00001006797	PBMCs isolated from 27 individuals (11 narcolepsy type 1 patients, 16 healthy controls) were stimulated with the peptide Neuroaminidase 175-189 or Protein-O-mannosyl transferase 1 (POMT1) 675-689 or media as control. FACS sorted CD4+ and CD8+ lymphocytes from one patient were subjected to the same stimulation. Transcriptome profiling was done with a 3' tagging protocol. T cell receptor repertoires were profiled with amplicon sequencing (Rep-seq). The dataset contains FASTQ files with sequencing reads, transcript count matrices and TCR clonotypes.	Illumina MiSeq NextSeq 500	82

Publications	Citations
Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1. Vuorela A, Freitag TL, Leskinen K, Pessa H, Härkönen T, Stracenski I, Kirjavainen T, Olsen P, Saarenpää-Heikkilä O, Ilonen J, Knip M, Vaheri A, Partinen M, Saavalainen P, Meri S, Vaarala O. Nat Commun 12: 2021 2283	15