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- Title
Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.
- Authors
Ambati, A.; Poiret, T.; Svahn, B.‐M.; Valentini, D.; Khademi, M.; Kockum, I.; Lima, I.; Arnheim‐Dahlström, L.; Lamb, F.; Fink, K.; Meng, Q.; Kumar, A.; Rane, L.; Olsson, T.; Maeurer, M.
- Abstract
Background Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. Objective The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma ( IFNγ) production from immune cells in response to molecularly defined targets. Methods Cellular reactivity defined by IFNγ production was examined in blood from 38 ( HLA- DQB1*06:02+) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA- DQB1*06:02+ and 53 HLA- DQB1*06:02−) control subjects, matched for age, sex and exposure, using a variety of different antigens: β-haemolytic group A streptococcal ( GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets ( CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). Results IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 ( P = 0.0065) and streptodornase B protein ( P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine ( IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher ( P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. Conclusion β-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.
- Subjects
NARCOLEPSY; STREPTOCOCCUS; IMMUNE response; DROWSINESS; CATAPLEXY; HEMOLYSIS &; hemolysins
- Publication
Journal of Internal Medicine, 2015, Vol 278, Issue 3, p264
- ISSN
0954-6820
- Publication type
Article
- DOI
10.1111/joim.12355