Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 33863907.
- Also identified by DOI 10.1038/s41467-021-22637-8 and PMC identifier 8052463.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA<sub>175-189</sub>) and nucleoprotein 214-228 (NP<sub>214-228</sub>), but also respond to a NA<sub>175-189</sub>-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1<sub>675-689</sub>). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA<sub>175-189</sub> or POMT1<sub>675-689</sub>. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.
Medical subject headings
- Influenza A Virus, H1N1 Subtype
- Influenza Vaccines
- Influenza, Human
- Mannosyltransferases
- Narcolepsy