tetano
Editor, Senior Moderator
J Intern Med. 2015 Feb 14. doi: 10.1111/joim.12355. [Epub ahead of print]
[h=1]Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.[/h] Ambati A[SUP]1[/SUP], Poiret T, Svahn BM, Valentini D, Khademi M, Kockum I, Lima I, Arnheim-Dahlstr?m L, Lamb F, Fink K, Meng Q, Kumar A, Rane L, Olsson T, Maeurer M.
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]OBJECTIVE:[/h] The aim of this study was to investigate potential aetiological factors in Swedish cases of post-vaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets.
[h=4]METHODS:[/h] Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02[SUP]+[/SUP] ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02[SUP]+[/SUP] and 53 HLA-DQB1*06:02[SUP]-[/SUP] ) 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), non-influenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue).
[h=4]RESULTS:[/h] IFNγ 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 anti-streptolysin O were observed in narcolepsy cases, compared to vaccinated controls.
[h=4]CONCLUSION:[/h] 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 IFNγ cellular immune response. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Streptococcus ; Pandemrix; Streptolysin; T cells; interferon-gamma; narcolepsy
PMID: 25683265 [PubMed - as supplied by publisher]
[h=1]Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.[/h] Ambati A[SUP]1[/SUP], Poiret T, Svahn BM, Valentini D, Khademi M, Kockum I, Lima I, Arnheim-Dahlstr?m L, Lamb F, Fink K, Meng Q, Kumar A, Rane L, Olsson T, Maeurer M.
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]OBJECTIVE:[/h] The aim of this study was to investigate potential aetiological factors in Swedish cases of post-vaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets.
[h=4]METHODS:[/h] Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02[SUP]+[/SUP] ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02[SUP]+[/SUP] and 53 HLA-DQB1*06:02[SUP]-[/SUP] ) 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), non-influenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue).
[h=4]RESULTS:[/h] IFNγ 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 anti-streptolysin O were observed in narcolepsy cases, compared to vaccinated controls.
[h=4]CONCLUSION:[/h] 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 IFNγ cellular immune response. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Streptococcus ; Pandemrix; Streptolysin; T cells; interferon-gamma; narcolepsy
PMID: 25683265 [PubMed - as supplied by publisher]