A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009–2010

• Published in: Journal of autoimmunity 2014-05, Vol.50 (Jan 28), p.99-106
• Main Authors: Lind, Alexander, Ramelius, Anita, Olsson, Tomas, Arnheim-Dahlström, Lisen, Lamb, Favelle, Khademi, Mohsen, Ambati, Aditya, Maeurer, Markus, Nilsson, Anna-Lena, Bomfim, Izaura Lima, Fink, Katharina, Lernmark, Åke
• Format: Article
• Language: English
• Subjects: A/H1N1; Adolescent; Adult; Aged; Allergy and Immunology; Antibodies, Viral - blood; Autoantibodies; Autoantibodies - blood; Autoimmunity; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases; Child; Child, Preschool; Clinical Medicine; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Glutamate Decarboxylase - antagonists & inhibitors; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - immunology; HLA-DQ beta-Chains - genetics; HLA-DQ beta-Chains - immunology; HLA-DQB106:02; Humans; Influenza A Virus, H1N1 Subtype - immunology; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Narcolepsy; Narcolepsy - chemically induced; Narcolepsy - diagnosis; Narcolepsy - genetics; Narcolepsy - immunology; Nervous system (semeiology, syndromes); Neurology; Pandemics - prevention & control; Reumatologi och inflammation; Rheumatology and Autoimmunity; Sweden; Vaccination; Vaccination - adverse effects
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2014.01.031

Abstract Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix® . A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6–69 years of age) and 80 healthy controls (3–61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [35 S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls ( p  = 0.006). A/H1N1 antibody levels were higher among the