0627 Influenza HA Antibody Titers in Recent Onset Type-1 Narcolepsy

Abstract Introduction 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. We tested whether recent onset type 1 narcolepsy patients have increased influenza antibody titers comparing with matched HLA-DQB1*0602 positive controls. Methods Sera of 82 recent onset type-1 narcolepsy patients (12 [1-25] months) and 84 healthy controls matched by sex, age, and year and season of sample collection were used. Sera were tested for Influenza-A and B HA antibodies using hemagglutinin inhibition (HAI) assays against the dominant strains known to circulate at time of collection. HAI assays against H1N1pdm09 were also tested independently in samples collected after 2009. Antibody titers were log2 transformed into geometric mean, 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 regression and logistic regression were done to analyze association between confounding factors and disease status and HA antibody titers. Results H1N1pdm09 HA titers were increased in 25/63 (39.7%) subjects collected after 2009. Increasing HA titers (doubling rate) of H1N1pdm09 [OR=1.2962(1.0513, 1.5984), p=0.015], all H1N1 [OR=1.13(1.03-1.24), p=0.023] and B/Victoria [1.37 (1.16-1.61), p=0.001] were associated with narcolepsy, whereas no association was found with H3N2 and B/Yamagata. Logistic regression shows after controlling sex, age and season of sample collection, narcolepsy is associated with H1N1pdm09 [4.68(1.5281, 14.3392), p=0.007] and B/Victoria strains [5.5306 (2.6039, 11.8224), p=0.001]. Conclusion 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. Support (if any) This work was supported by 5R01AI144798-03/HHS|NIH|National Institute of Allergy and Infectious Diseases (NIAID).