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

被引:20
作者
Ambati, A. [1 ,2 ]
Poiret, T. [3 ]
Svahn, B. -M. [2 ]
Valentini, D. [2 ]
Khademi, M. [4 ]
Kockum, I. [4 ]
Lima, I. [4 ]
Arnheim-Dahlstrom, L. [5 ]
Lamb, F. [5 ]
Fink, K. [4 ]
Meng, Q. [3 ]
Kumar, A. [6 ]
Rane, L. [3 ]
Olsson, T. [4 ]
Maeurer, M. [2 ,3 ]
机构
[1] Karolinska Inst, Dept Med, S-10401 Stockholm, Sweden
[2] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Solna, Sweden
[3] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, S-10401 Stockholm, Sweden
[4] Karolinska Inst, Dept Clin Neurosci, S-10401 Stockholm, Sweden
[5] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden
[6] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy
基金
瑞典研究理事会;
关键词
interferon-gamma; narcolepsy; Pandemrix; Streptococcus; streptolysin; T cells; EPSTEIN-BARR-VIRUS; TUMOR-NECROSIS-FACTOR; HUMAN T-CELLS; AUTOIMMUNE-DISEASE; MOLECULAR MIMICRY; M-PROTEINS; IN-VITRO; HLA-DR; ANTIBODIES; MULTIPLE;
D O I
10.1111/joim.12355
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundType 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. ObjectiveThe aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFN) production from immune cells in response to molecularly defined targets. MethodsCellular reactivity defined by IFN 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: -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). ResultsIFN- 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, IFN, 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-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- cellular immune response.
引用
收藏
页码:264 / 276
页数:13
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