Anti-ganglioside antibodies in Pandemrix®-induced narcolepsy
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1
Haartman Institute, University of Helsinki, Finland, Department on Immunology and Bacteriology, Finland
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2
National Institute for Health and Welfare, Helsinki, Finland, Department of Vaccines and Immune Protection,, Finland
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3
Sleep Clinic, Finnish Narcolepsy Research Centre, Vitalmed Research Centre Helsinki, Finland, Finland
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4
University of Helsinki, Helsinki, Finland, Department of Clinical Neurosciences, Finland
Narcolepsy with cataplexy (NC) is a chronic, neurological disease with an unknown etiology. It is caused by a selective loss of hypocretin-producing neurons in hypothalamus. This causes the typical symptoms of the disease: various sleep and metabolic disorders, cataplexy and hallucinations. NC is considered as an autoimmune disease, where genetic and environmental risk factors contribute to its development.
NC has a strong association with HLA-DQB1*0602 (DQ6), and recent reports from several European countries have confirmed an association between the adjuvanted H1N1 Pandemrix® vaccine and NC in genetically susceptible children and adolescents. However, the triggering role of the vaccine components and the mechanisms behind the disease remain unsolved.
We studied the role of humoral immunity in the pathogenesis of Pandemrix-narcolepsy by screening anti-neuronal antibodies from patients’ sera. No antibodies were detected against the neuronal antigens (Hu, Ri, Yo, Tr, MAG, myelin, Ma/Ta, GAD, amphiphysin, aquaporin-4, NMDAR, AMPA-type glutamate receptor, glycine receptor, CASPR2 and LGI1) in patient sera (n=5). However, when sera of Pandemrix-narcolepsy patients (n=20) were screened for 12 anti-ganglioside antibodies (AGA) by line immunoassay a high frequency of (>30%) of AGA (IgG or/and IgM) were found. No AGA were detected in the control sera of healthy unvaccinated children (n=6). The majority of the found AGAs (IgG) were against gangliosides GM4, GM3 and GD3. Our results suggest that humoral immunity is involved in the pathogenesis of Pandemrix-narcolepsy, and that AGA could cause at least part of the neuronal damage of the disease.
Keywords:
Narcolepsy,
H1N1,
ganglioside,
Neuron,
Pandemrix vaccination
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Saariaho
A,
Vaarala
O,
Partinen
M and
Meri
S
(2013). Anti-ganglioside antibodies in Pandemrix®-induced narcolepsy.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01075
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Received:
30 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Anna-Helena Saariaho, Haartman Institute, University of Helsinki, Finland, Department on Immunology and Bacteriology, Helsinki, Finland, anna-helena.saariaho@helsinki.fi