Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

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.

• Authors: A Ambati, T Poiret, B-M Svahn, D Valentini, M Khademi, I Kockum, I Lima, L Arnheim-Dahlström, F Lamb, K Fink, Q Meng, A Kumar, L Rane, T Olsson, M Maeurer
• Journal: Journal of internal medicine (J Intern Med) Vol. 278 Issue 3 Pg. 264-76 (Sep 2015) ISSN: 1365-2796 [Electronic] England
• PMID: 25683265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Association for the Publication of the Journal of Internal Medicine.

Chemical References

• Peptide Fragments
• interferon gamma (1-39)
• Interferon-gamma
• Antistreptolysin
• Streptodornase and Streptokinase

Topics

• Adolescent
• Adult
• Aged
• Antistreptolysin (blood)
• Child
• Female
• Humans
• Interferon-gamma (biosynthesis, blood)
• Male
• Middle Aged
• Narcolepsy (epidemiology, immunology)
• Peptide Fragments (biosynthesis, blood)
• Serotyping
• Streptococcus agalactiae (enzymology, immunology)
• Streptodornase and Streptokinase (immunology)
• Sweden (epidemiology)