Page 37 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Discussion
The associations between HLA-DQB1 alleles and NT1 in this large Dutch cohort have not significantly changed since the H1N1 pandemic in 2009 and the vaccination program following the pandemic. The percentage of NT1 patients that is homozygous for HLA-DQB1*06:02 has remained unchanged and this strongly argues against considering sporadic and H1N1 NT1 to be separate entities with a separate (immune) aetiology.
One study in a Chinese cohort comparing HLA-DQB1-associations in pre- and post-H1N1 NT1 patients found a decrease in the percentage of NT1 patients that was homozygous for HLA-DQB1*06:02 since the 2009 H1N1 pandemic (Han et al., 2013). Differences in HLA-associations in populations from different ethnic background have been reported (Mignot et al., 2001), which may explain these contradictory findings. The positive association between NT1 and HLA- DQ7 and HLA-DQB1*05:02 persist after the H1N1 pandemic. The same goes for negative associations between NT1 and HLA-DQ2, HLA-DQB1*05:01 and HLA-DQB1*06:03.
These findings are in line with those of two recent reports describing these associations in small numbers of post-H1N1 NT1 patients that report positive associations of post-H1N1 with HLA-DQ7 and negative associations with HLA-DQ2 (Lind et al., 2019, Juvodden et al., 2019b). Both these and other studies in NT1 patients before and after the H1N1 pandemic also describe the same associations that we found (Mignot et al., 2001, van der Heide et al., 2015b, Hong et al., 2007, Tafti et al., 2014, Bomfim et al., 2017, Tafti et al., 2016, Han et al., 2013).
The negative association between NT1 and DQB1*06:01 previously reported (Mignot et al., 2001, Hong et al., 2007), were not replicated in the current study. This might be explained by the abundancy of this HLA-DQ allele in the Asian population, compared to the almost absence of this allele in people of European ancestry. Other associations of NT1 (either positive or negative), with HLA- DQ8 (Hong et al., 2007, Bomfim et al., 2017), HLA-DQB1*06:04 (Hong et al., 2007) and HLA-DQB1*06:09 (Tafti et al., 2014, Bomfim et al., 2017) were also not replicated in the current study.
HLA associations after 2009 H1N1 pandemic
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