Risks of neurological and immune‐related diseases, including narcolepsy, after vaccination with Pandemrix: a population‐ and registry‐based cohort study with over 2 years of follow‐up

Persson, Ingemar; Granath, Fredrik; Askling, Johan; Ludvigsson, Jonas F.; Olsson, Tomas; Feltelius, Nils

doi:10.1111/joim.12581

Cited by 42 publications

(78 citation statements)

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“…38 The specific disease mechanisms underlying this new HLA-DP association in narcolepsy remain elusive. Narcolepsy was recently associated with pandemic H1N1 2009 vaccination [11][12][13][14][15][16][17] and infections. 8,10 In addition, streptococcal antibodies were found more frequently in narcoleptics than in matched healthy control individuals.…”

Section: Discussionmentioning

confidence: 99%

“…5,10 Further, vaccination with Pandemrix, an AS03-adjuvanted pandemic H1N1 vaccine approved for use in Europe, was associated with a 3-to 17-fold increased risk of developing childhood narcolepsy in multiple countries, leading to increased incidence in Scandinavia. [11][12][13][14][15][16][17] For unclear reasons, increased risk of narcolepsy after the use of other H1N1 vaccines has not been reported, and is unlikely to be as strong as that following Pandemrix. 18 These findings, together with genetic evidence, suggest that narcolepsy is an autoimmune disease affecting hypocretin neurons and triggered by upper-airway infections.…”

Section: Introductionmentioning

confidence: 99%

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HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Ollila

Ravel

Han

et al. 2015

The American Journal of Human Genetics

125

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Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Ollila

Ravel

Han

et al. 2015

The American Journal of Human Genetics

125

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“…In parallel, several Scandinavian countries (first Sweden and Finland later also Ireland and Norway) started their own rapid assessment studies, to be able to respond quickly to fierce political pressure and the public concerns, while being personally threatened by the public [15][16][17][18][19][20]. Most of these rapid assessment studies focused on children/adolescents as the signal had arisen in this group.…”

Section: How the Narcolepsy Signal Was Followed Upmentioning

confidence: 99%

The narcolepsy-pandemic influenza story: Can the truth ever be unraveled?

Sturkenboom

2015

Vaccine

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“…However, rare and unexpected adverse events may not be seen until vaccines are administered to a large population. One formulation of adjuvanted, split-virion, inactivated H1N1pdm vaccine marketed in Europe was associated with an increased incidence of narcolepsy in children and young adults [110][111][112][113][114][115][116][117]. Interestingly, a different formulation of AS03-adjuvanted monovalent H1N1pdm vaccine [118,119] and other monovalent H1N1pdm vaccines were not associated with narcolepsy [102,120,121].…”

Section: Are Pandemic Influenza Vaccines Safe and Immunogenic?mentioning

confidence: 99%

Refining the Approach to Vaccines Against Influenza a Viruses with Pandemic Potential

Czakó

Subbarao

2015

Future Virol.

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Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.

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Risks of neurological and immune‐related diseases, including narcolepsy, after vaccination with Pandemrix: a population‐ and registry‐based cohort study with over 2 years of follow‐up

Cited by 42 publications

References 1 publication

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

The narcolepsy-pandemic influenza story: Can the truth ever be unraveled?

Refining the Approach to Vaccines Against Influenza a Viruses with Pandemic Potential

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