Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus

Saariaho, Anna Helena; Vuorela, Arja; Freitag, Tobias; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

doi:10.1016/j.jaut.2015.07.006

Cited by 47 publications

(28 citation statements)

References 51 publications

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“…In these regions, the onset of narcolepsy was observed following vaccination with Pandemrix, an adjuvanted pH1N1 vaccine. A recent report has identified the presence of autoantibodies against ganglioside GM3 in Pandemrix-vaccinated children who developed narcolepsy with cataplexy [87], providing additional support for the theory that influenza-associated narcolepsy is autoimmune, and suggesting an underlying mechanism similar to GBS. Markers of inflammation (interferon gamma, CCL11, IL12) identified by Luminex assay have been associated with onset of narcolepsy [88].…”

Section:  Narcolepsymentioning

confidence: 84%

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Moise

Beseme

Tassone

et al. 2016

Expert Review of Vaccines

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SummaryT cells are extensively trained on 'self' in the thymus and then move to the periphery, where they seek out and destroy infections and regulate immune response to self-antigens. T cell receptors (TCR) on T cells' surface recognize T cell epitopes, short linear strings of amino acids presented by antigen-presenting cells. Some of these epitopes activate T effectors, while others activate regulatory T cells. It was recently discovered that T cell epitopes that are highly conserved on their TCR face with human genome sequences are often associated with T cells that regulate immune response. These TCR-cross-conserved or 'redundant epitopes' are more common in proteins found in pathogens that have co-evolved with humans than in other noncommensal pathogens. Epitope redundancy might be the link between pathogens and autoimmune disease. This article reviews recently published data and addresses epitope redundancy, the "elephant in the room" for vaccine developers and T cell immunologists.

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Section:  Narcolepsymentioning

confidence: 84%

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Moise

Beseme

Tassone

et al. 2016

Expert Review of Vaccines

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“…Furthermore Ahmed et al found, in Pandemrix vaccinated patients, antibodies to influenza nucleoprotein cross-reacting with human hypocretin receptor 2, which could explain the narcolepsy associated with Pandemrix vaccination [24]. Finally, in the same direction, Saariaho et al described autoantibodies against ganglioside GM3 associated to narcolepsy after Pandemrix vaccination [37]. …”

Section: Discussionmentioning

confidence: 99%

Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells

et al. 2017

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Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.

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“…This is well illustrated by the fact of serum antiganglioside antibodies, often detected although their levels decrease over time [14] which may represent a Downloaded by [La Trobe University] at 08:26 15 June 2016 good candidate biomarker in this complex condition, despite their limited sensitivity particularly in patients with AMAN and virtual absence in AIDP [15]. …”

mentioning

confidence: 99%

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

Jasti

Selmi

Sarmiento-Monroy

et al. 2016

Expert Review of Clinical Immunology

118

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Guillain-Barré syndrome is a rare disease representing the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month. The etiology and pathogenesis remain largely enigmatic and the syndrome results in death or severe disability in 9-17% of cases despite immunotherapy. Areas covered: In terms of etiology, Guillain-Barré syndrome is linked to Campylobacter infection but less than 0.1% of infections result in the syndrome. In terms of pathogenesis, activated macrophages and T cells and serum antibodies against gangliosides are observed but their significance is unclear. Expert commentary: Guillain-Barré syndrome is a heterogeneous condition with numerous subtypes and recent data point towards the role of ganglioside epitopes by immunohistochemical methods. Ultimately, the syndrome results from a permissive genetic background on which environmental factors, including infections, vaccination and the influence of aging, lead to disease.

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Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus

Cited by 47 publications

References 51 publications

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

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