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

来源：

JOURNAL OF INTERNAL MEDICINE | 2015年 / 278卷 / 03期

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

页码：264 / 276

页数：13

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