Han Yan1, Bruna de Freitas Dias2, Ling Lin1, Jing Zhang1, Giorgio Ricciardiello Mejia1, Emmanuel Mignot1
1Center for Narcolepsy, Department of Psychiatry and Behavioral Science, Stanford University, Stanford, CA, United States, 2Department of Neurology, Stanford University, Stanford, CA, United States
Objective:
To test whether recent onset type-1 narcolepsy patients have increased flu antibodies titers comparing with well-matched controls.
Background:
Epidemiological studies have shown associations between pandemic H1N1 2009 influenza-A infection and vaccination (only using Pandemrix®) and the onset of narcolepsy, an autoimmune disease associated with HLA-DQB1*0602.
Design/Methods:
Sera of 173 recent-onset type-1 narcolepsy patients (12 [1-25] months) and 185 healthy controls matched by sex, age, and year and season of sample collection were used. Sera were tested for Influenza-A and B antibodies using hemagglutinin inhibition (HAI) assays and neuraminidase inhibition (NAI) assay against the dominant strains known to circulate at the time of collection. Antibody titers were log2 transformed to geometric mean titers (GMT), with zero being <1/10 dilution, 1 as 1/10, 2 as 1/20, etc., so that every dilution represents an increment of 1 unit. Further analysis using multiple variable linear and logistic regression were done to analyze the association between confounding factors and disease status and HA/NA antibody titers.
Results:
Increasing GMT of HA antibody against H1N1pdm09 [OR=1.77(1.001, 3.10), p=0.05], H1N1pre2009 [OR=2.32(1.21-4.44), p=0.01] and B/Victoria [3.63 (1.17-11.1), p=0.03] was associated with narcolepsy by logistic regression. For NA antibodies, elevated GMT of NA antibody against H1N1pdm09 [β-coefficient=1.27(0.56, 1.99), p=0.001], and B/Victoria [β-coefficient=1.28 (0.74-1.83), p=0.00] was found in patients by multivariate linear regression, whereas no association was found with HA and/or NA antibodies against H3N2 and B/Yamagata. HA and NA antibody titers against different strains on the same samples were weakly correlated (Pearson coefficient [-0.01 – 0.26] ).
Conclusions:
Both H1N1 and B/Victoria, but not other strains, may trigger narcolepsy onset. This result is in line with a recent epidemiological study in Europe that reported a strong increase in narcolepsy onset in 2010 (following 2009 H1N1 pandemic) and a secondary peak in 2013 following a season with a dominant B/Victoria infection.
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