Multiple Sclerosis and Infectious Childhood Diseases

Bachmann, Stefan; Kesselring, Jürg

doi:10.1159/000026167

Cited by 42 publications

(27 citation statements)

References 21 publications

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“…This action of PTx may certainly contribute to the immunological adjuvant effect of PTx. PTx is a major virulence factor of B. pertussis, and infection by this pathogen was reported to be capable of being an initiation or developmental factor of autoimmune disease (46,47). Thus, our findings may represent a novel mechanism by which this environmental microbial toxin can promote autoimmunity.…”

Section: Discussionmentioning

confidence: 65%

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

Chen

Howard

Oppenheim

2007

The Journal of Immunology

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Compelling evidence has now demonstrated that IL-17-producing CD4 cells (Th17) are a major contributor to autoimmune pathogenesis, whereas CD4+CD25+ T regulatory cells (Treg) play a major role in suppression of autoimmunity. Differentiation of proinflammatory Th17 and immunosuppressive Treg from naive CD4 cells is reciprocally related and contingent upon the cytokine environment. We and others have reported that in vivo administration of pertussis toxin (PTx) reduces the number and function of mouse Treg. In this study, we have shown that supernatants from PTx-treated mouse splenic cells, which contained IL-6 and other proinflammatory cytokines, but not PTx itself, overcame the inhibition of proliferation seen in cocultures of Treg and CD4+CD25− T effector cells. This stimulatory effect could be mimicked by individual inflammatory cytokines such as IL-1β, IL-6, and TNF-α. The combination of these cytokines synergistically stimulated the proliferation of CD4+CD25− T effector cells despite the presence of Treg with a concomitant reduction in the percentage of FoxP3+ cells and generation of IL-17-expressing cells. PTx generated Th17 cells, while inhibiting the differentiation of FoxP+ cells, from naive CD4 cells when cocultured with bone marrow-derived dendritic cells from wild-type mice, but not from IL-6−/− mice. In vivo treatment with PTx induced IL-17-secreting cells in wild-type mice, but not in IL-6−/− mice. Thus, in addition to inhibiting the development of Treg, the immunoadjuvant activity of PTx can be attributable to the generation of IL-6-dependent IL-17-producing CD4 cells.

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Section: Discussionmentioning

confidence: 65%

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

Chen

Howard

Oppenheim

2007

The Journal of Immunology

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“…It has been proposed that some infections increase the risk for MS if acquired in late childhood or adulthood, but are less harmful and may even confer protective immunity if acquired in infancy [42,43] . However, powerful studies using data from the well-known Danish registries and thus immune to recall bias did not find any effect of age of infection and risk of MS [17,19] emphasizing the need to account for recall and reporting biases, including gender.…”

Section: Discussionmentioning

confidence: 99%

Association of Infectious Mononucleosis with Multiple Sclerosis

et al. 2009

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Background: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS. Methods: Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Results: Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71–2.48). Females were more aware of disease history than males (p < 0.001). Conclusions: The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.

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“…People with an increased predisposition to autoimmune diseases might have a higher risk of developing MS (1,58). Viral infection has long been considered as one of the causes of MS (1,(58)(59)(60)(61)(62) and viruses, such as measles, herpes, EBV, hepatitis, and influenza, and the bacterium Chlamydia pneumoniae have been shown to be associated with MS (63)(64)(65)(66). It will be interesting to determine whether CSF samples with anti-GAPDH IgG contain Abs that react with the GAPDH of these viruses.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Glyceraldehyde-3-Phosphate Dehydrogenase Activity by Antibodies Present in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

Kölln

Zhang

Thai

et al. 2010

The Journal of Immunology

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We have previously shown that B cells and Abs reactive with GAPDH and antitriosephosphate isomerase (TPI) are present in lesions and cerebrospinal fluid (CSF) in multiple sclerosis (MS). In the current study, we studied the effect of anti-GAPDH and anti-TPI CSF IgG on the glycolytic enzyme activity of GAPDH and TPI after exposure to intrathecal IgG from 10 patients with MS and 34 patients with other neurologic diseases. The degree of inhibition of GAPDH activity by CSF anti-GAPDH IgG in the seven MS samples tested varied from 13 to 98%, which seemed to correlate with the percentage of anti-GAPDH IgG in the CSF IgG (1–45%). Inhibition of GAPDH activity (18 and 23%) by CSF IgG was seen in two of the 34 patients with other neurologic diseases, corresponding to the low percentage of CSF anti-GAPDH IgG (1 and 8%). In addition, depletion of anti-GAPDH IgG from CSF IgG, using immobilized GAPDH, removed the inhibitory effect of the IgG on GAPDH. No inhibition of GAPDH activity was seen with CSF samples not containing anti-GAPDH IgG. No inhibition of TPI activity was seen with any purified CSF IgG sample. These findings demonstrate an increased percentage of anti-GAPDH Abs in the CSF of patients with MS that can inhibit GAPDH glycolytic enzyme activity and may contribute to neuroaxonal degeneration.

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Multiple Sclerosis and Infectious Childhood Diseases

Cited by 42 publications

References 21 publications

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

Association of Infectious Mononucleosis with Multiple Sclerosis

Inhibition of Glyceraldehyde-3-Phosphate Dehydrogenase Activity by Antibodies Present in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

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