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Linking Narcolepsy to the Flu?

Gert van der Hoek

In Memoriam - Editor, Senior Moderator
Linking Narcolepsy to the Flu? Researchers Make Progress Identifying Molecular Mimicry

[FONT=&quot]Published on February 1, 2019


One day, Claire Crisp told her daughter to meet her in the car, but when Crisp walked outside she found her three-year-old, Mathilda, asleep, facedown on the pavement in front of the family?s minivan.

In the months that followed, the child collapsed on the kitchen floor, just missing the knives sticking up in the dishwasher. She fell asleep in the bathtub, in the swimming pool, and at the beach.

?We were deeply concerned,? says Crisp.

After a whirlwind of doctor?s visits and hospital stays, Mathilda was diagnosed in 2010 with narcolepsy. She was one of a wave of new cases in Europe during the global swine flu outbreak. There are still questions about whether the H1N1 Pandemrix vaccine could have contributed. Mathilda?s mother thinks so.

Now research from Stanford University sheds light on the mechanism by which either contracting the flu or receiving the swine flu vaccine could trigger an immune reaction that may lead to narcolepsy. The study, published in Proceedings of the National Academy of Sciences, also provides a specific example that demonstrates the theory in immunology called molecular mimicry, that autoimmunity is the result of the immune system mistaking healthy cells in a person?s body for proteins within infectious pathogens.

In this case, the research reveals the mechanism behind how the immune system can wreak havoc on the brains of people with narcolepsy, confusing a chemical in the nervous system that is responsible for wakefulness with a protein in some strains of influenza and in some versions of the swine flu vaccine.
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Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy

Significance

[FONT=&quot]This work shows that the amidated terminal ends of the secreted hypocretin (HCRT) peptides (HCRTNH2) are autoantigens in type 1 narcolepsy, an autoimmune disorder targeting HCRT neurons.

The autoimmune process is usually initiated by influenza A flu infections, and a particular piece of the hemagglutinin (HA) flu protein of the pandemic 2009 H1N1 strain was identified as a likely trigger. This HA epitope has homology with HCRTNH2 and T cells cross-reactive to both epitopes are involved in the autoimmune process by molecular mimicry.

Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.
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