<i>Staphylococcus aureus</i> harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations

Mulvey, Michael R.; Doupe, Malcolm; Prout, Michael; Leong, Christine; Hizon, Romeo; Grossberndt, Amy; Klowak, Meghann; Gupta, Aneri; Melanson, Maria; Gomori, Andrew; Esfahani, Farid; Klassen, Loressa; Frost, Emma E.; Namaka, Michael

doi:10.1177/1352458510391343

Cited by 43 publications

(39 citation statements)

References 29 publications

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“…RA patients were shown to carry different S. aureus types compared to HC and had higher IgG levels against TSST-134. More recently, relapsing MS patients were shown to carry S. aureus isolates positive for the SAg gene sea more frequently than non-relapsing MS patients35. However, in the present study no apparent associations between clinical data of GPA patients and particular S. aureus types were found.…”

Section: Discussioncontrasting

confidence: 72%

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Glasner

Timmeren

Stobernack

et al. 2015

Sci Rep

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Chronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as healthy carriers, nor whether specific S. aureus types are associated with GPA. Therefore, this study was aimed at assessing humoral immune responses of GPA patients against S. aureus antigens in relation to the genetic diversity of their nasal S. aureus isolates. A retrospective cohort study was conducted, including 85 GPA patients and 18 healthy controls (HC). Humoral immune responses against S. aureus were investigated by determining serum IgG levels against 59 S. aureus antigens. Unexpectedly, patient sera contained lower anti-staphylococcal IgG levels than sera from HC, regardless of the patients' treatment, while total IgG levels were similar or higher. Furthermore, 210 S. aureus isolates obtained from GPA patients were characterized by different typing approaches. This showed that the S. aureus population of GPA patients is highly diverse and mirrors the general S. aureus population. Our combined findings imply that GPA patients are less capable of mounting a potentially protective antibody response to S. aureus than healthy individuals.

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Section: Discussioncontrasting

confidence: 72%

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Glasner

Timmeren

Stobernack

et al. 2015

Sci Rep

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“…These autoreactive T cells are generated in the periphery and cross the blood-brain barrier to the brain parenchyma where they initiate an autoimmune attack on the myelin sheath [1,2]. MS has been histopathologically characterized by four main findings: inflammation, demyelination, axonal damage and gliosis.…”

Section: Introductionmentioning

confidence: 99%

“…This disease can be induced in a variety of animals, particularly in rodents, providing models of acute monophasic, relapsing remitting and chronic progressive CNS inflammation [2]. Although many gaps still exist in the understanding of MS immunopathogenesis, it is widely believed that this complex pathology involves both host genetic and environmental factors [1]. Infectious disease agents can modulate autoimmune diseases in many different ways, such as triggering these pathologies or, contrarily, preventing their development [3,4].…”

Section: Introductionmentioning

confidence: 99%

Previous infection with Staphylococcus aureusstrains attenuated experimental encephalomyelitis

et al. 2014

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BackgroundBacterial superantigens are potent T cell activators that can activate T cells with specificity for antigens of the central nervous system (CNS). In this study, we compared the effect of two S. aureus strains on experimental autoimmune encephalomyelitis (EAE) development. C57BL/6 female mice were infected with S. aureus ATCC 51650, which produces toxic shock syndrome toxin 1 (TSST-1+) or S. aureus ATCC 43300, which does not produce toxins (TOX-). Three days later, the animals were subjected to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG). The weight variation, disease incidence and clinical score were recorded daily. Cytokines and Foxp3+ regulatory T cells in the brain were evaluated during the acute disease phase. Cytokines and Foxp3+ regulatory T cells in the spleen and histopathological analysis of the CNS were assessed during the chronic stage.ResultsPrevious infection with both strains similarly decreased the clinical score; however, only the TSST-1+ strain clearly diminished inflammation in the CNS. The infections also modulated cytokine production in the spleen and CNS. Reduced production of IL-5 and IL-10 was detected in MOG-stimulated spleen cultures in the TOX- and TSST-1+ infected groups, respectively. In S. aureus stimulated cultures, there was an increased production of IFN-γ and IL-10 in both infected groups and an increased level of IL-5 in the TSST-1+ group. CNS infiltrating cell cultures from previously infected mice produced less IL-17 in response to MOG and more IFN-γ in response to S. aureus stimulation.ConclusionsThese results indicated that both strains attenuated clinical EAE manifestations, but only TSST-1 clearly decreased CNS inflammation.

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“…Another hypothesis emerging from animal models suggests that bacterial superantigens (e.g., Staphylococcus aureus enterotoxins A, B, C, D, and E) activate auto-reactive T cells, which then promotes the onset of immune diseases like MS (Brocke et al, 1993). Indeed, a significant proportion of patients with relapsing MS (within 30 days) were positive for S. aureus enterotoxin A as compared to subjects without MS (Mulvey et al, 2011). For viruses, several mechanisms of demyelination have been proposed, including viral lysis of infected oligodendrocytes or immune lysis of uninfected oligodendrocytes specifically or non-specifically triggered by the viral infection (reviewed in Libbey et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid in a Small Cohort of Patients with Multiple Sclerosis Was Generally Free of Microbial DNA

Jovel

OʼKeefe

Patterson

et al. 2017

Front. Cell. Infect. Microbiol.

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Multiple sclerosis (MS) is a common cause of non-traumatic neurologic disability with high incidence in many developed countries. Although the etiology of the disease remains elusive, it is thought to entail genetic and environmental causes, and microbial pathogens have also been envisioned as contributors to the phenotype. We conducted a metagenomic survey in cerebrospinal fluid (CSF) from 28 MS patients and 15 patients suffering other type of neurological conditions. We detected bacterial reads in eight out of the 15 non-MS patients and in a single MS patient, at an abundance >1% of total classified reads. Two patients were of special interest: one non-MS patient harbored ~73% bacterial reads, while an MS patient had ~83% bacterial reads. In the former case, Veillonella parvula, a bacterium occasionally found associated with meningitis was the predominant species, whilst Kocuria flava, apparently an environmental bacterium, predominated in the latter case. Thirty-four out of 43 samples contained <1% bacterial reads, which we regard as cross- or environmental contamination. A few viral reads corresponding to Epstein-Barr virus, cytomegalovirus, and parvovirus were also identified. Our results suggest that CSF of MS patients is often (but not always) free of microbial DNA.

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Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations

Abstract: The ability to rapidly screen patients for the presence of S. aureus producing sea may serve as a useful marker of a potential MS exacerbation.

Cited by 43 publications

References 29 publications

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Previous infection with Staphylococcus aureusstrains attenuated experimental encephalomyelitis

Cerebrospinal Fluid in a Small Cohort of Patients with Multiple Sclerosis Was Generally Free of Microbial DNA

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