Vaccination against infection in patients with multiple sclerosis

Loebermann, Micha; Winkelmann, Alexander; Hartung, Hans‐Peter; Hengel, Hartmut; Reisinger, Emil C.; Zettl, Uwe K.

doi:10.1038/nrneurol.2012.8

Cited by 91 publications

(67 citation statements)

References 72 publications

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“…Overall, epidemiological data do not support a role of these viruses in the pathogenesis of MS though some controversy still holds concerning the safety of HBV vaccination [19]–[23]. Interestingly, Gregory et al (2012) [24] demonstrated that in the TNFRSF1A gene, which is part of the HBV interactome, the MS-associated variant directs increased expression of a soluble tumor necrosis factor receptor 1.…”

Section: Discussionmentioning

confidence: 99%

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

et al. 2013

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Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

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Section: Discussionmentioning

confidence: 99%

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

et al. 2013

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“…However, randomized, double-blind, placebo-controlled studies during the past decade have shown that influenza vaccination of MS patients neither increases the relapse rate nor worsens the course of disease [51]. Indeed, the administration of standard vaccines in MS patients is considered safe worldwide, it follows the same recommendations as in healthy adults and actually should be recommended to MS patients in order to avoid attacks of the disease [52]. Having all this in mind, it cannot be excluded that our data on the reduced level of secreted Abs in response to TLR7 stimulation can have a role in the exacerbation of relapses observed in MS-affected individuals along episodes of influenza infection.…”

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confidence: 99%

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

et al. 2013

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The implication of B lymphocytes in the immunopathology of multiple sclerosis (MS) is increasingly recognized. Here we investigated the response of B cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored the frequency of TLR7-induced IgM and IgG-secreting cells in MS patients to the levels found in healthy donors, showing a specific deficiency in the TLR7 pathway. However, no difference was observed in the TLR9 response. Furthermore, in MS-derived PBMCs, TLR7-mediated production of IL-6 and the ex vivo expression of B-cell-activating factor of the TNF family, two crucial cytokines for B-cell differentiation and survival, were induced by IFN-β. Depletion of monocytes, which are key producers of both IL-6 and B-cellactivating factor of the TNF family, showed that TLR7-mediated B-cell differentiation into Ig-secreting cells is strongly dependent on the cross-talk between B cells and monocytes. Accordingly, impaired expression of TLR7 mRNA was observed in PBMCs and monocytes isolated from MS-affected individuals as compared with those from healthy donors, which was rescued by IFN-β therapy. Collectively, our data unveil a novel TLR7-regulated mechanism in in vivo IFN-β-stimulated whole leukocytes that could be exploited to define new TLR7-based strategies for the treatment of MS.Keywords: B cell r IFN-β r Monocyte r Multiple sclerosis r TLR Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionGrowing evidence is accumulating on the central role that B lymphocytes play in the immunopathology of multiple sclerosis (MS) [1,2]. For example, oligoclonal IgG bands, found in the cerebrospinal fluid of more than 90% of patients with MS, indicate an intrathecal Ab production [3]. The presence of clonally Correspondence: Dr. Eliana Marina Coccia e-mail: eliana.coccia@iss.it expanded B cells, plasma cells, complement and myelin-specific Abs in chronic MS lesions also suggested an intrathecal, Agdriven humoral immune response in the central nervous system of MS sufferers [4][5][6]. In addition, B-cell follicle-like structures are detectable in the meninges of MS patients [7,8]. More recently, B-cell depleting therapies, such as Rituximab (that targets the B lymphocyte surface antigen CD20 [9][10][11]), together with * These authors contributed equally to this work. Eur. J. Immunol. 2013Immunol. . 43: 1963Immunol. -1972 Ocrelizumab and Ofatumumab (two other humanized anti-CD20 monoclonal Abs), are proving their efficacy at various stages of clinical development [12]. All together these findings contribute to the compelling evidence that B cells and the humoral immune response are implicated in the pathogenesis of MS and suggest the therapeutic implications that all this may have for the treatment of this disease. B lymphocytes play an essential role in bridging innate and adaptive immunity. To differentiate into specialized cells capable of communicating with helper T cells and undergo Ab divers...

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“…However no substantial evidence has been found to refute its use and due to the protection that such a vaccine may provide, it is still in general use. The vaccine against yellow fever has been suggested to exacerbate MS [12,13] whereas tetanus vaccine might even have a protective effect on its clinical course [1,7,14]. The HLA-DR2 haplotype has demonstrated linkage and association with susceptibility to multiple sclerosis, especially after hepatitis B vaccination [15,16].…”

Section: Discussionmentioning

confidence: 99%

Balkans Syndrome: A Potential Link Between Multiple Sclerosis and Hypervaccination

Vacchiano

Vyshka

2012

J R Army Med Corps

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Balkans Syndrome is a recent term that has been widely used in the media to describe a heterogenous group of medical conditions that presented in soldiers following deployment on military operations to the former Yugoslavia and its neighbouring countries. These individuals had been subjected to an intense and protracted course of vaccinations (termed hypervaccination) prior to deployment, which has subsequently been implicated by the media as the cause of this disease. We describe the case of a 33-year old army officer, who received twenty vaccinations and boosters during the period 2000-2006, and was subsequently diagnosed with multiple sclerosis in 2008.

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Vaccination against infection in patients with multiple sclerosis

Cited by 91 publications

References 72 publications

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

IFN‐β therapy modulates B‐cell and monocyte crosstalk via TLR7 in multiple sclerosis patients

Balkans Syndrome: A Potential Link Between Multiple Sclerosis and Hypervaccination

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