Letter to the Editor

Ogasawara, Hitoshi; Kageyama, Michiaki; Yamaji, Katsuhiko; Takasaki, Yoshinari

doi:10.1177/0961203309106767

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…In this context, HERVs might act as both: encoding superantigens thereby result in enhanced inflammatory responses or mimicking self-antigens (Clausen, 2003; Rolland et al, 2006; Ogasawara et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Olival¹,

Faria²,

Nali³

et al. 2013

Front. Microbiol.

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Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5′ LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Olival¹,

Faria²,

Nali³

et al. 2013

Front. Microbiol.

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“…HERVs have been associated with schizophrenia and other psychiatric diseases in a number of studies (Dickerson et al, 2012; Huang et al, 2011; Karlsson et al, 2001; Lillehoj et al, 2000), and it is thought that HERV expression may induce an autoimmune state through molecular mimicry especially when coupled with viral or other infections (Brodziak et al, 2012; Leboyer et al, 2013; Ogasawara et al, 2010; Perron et al, 2012). A recent report of HERV-related immunoreactivity in plasmacytoid dendritic cells of the duodenum from patients with myalgic encephalomyelitis further links the gut to neuroinflammatory autoimmune processes by means of this retroelement mechanism (De Meirleir et al, 2013).…”

Section: Autoimmunity and Schizophreniamentioning

confidence: 99%

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Severance¹,

Yolken²,

Eaton

2016

Schizophrenia Research

210

149

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Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders.

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“…These proteins could be considered as “foreign” and could trigger B-cells to produce antibodies against them, which, in turn, might cross-react with other proteins of our bodies [1]. This mechanism is called “molecular mimicry” [1,38,39]. Some researchers point out that HERV-proteins may act as superantigens [35,36].…”

Section: Immunological Phenomena and Concepts Related To Pathogeneticmentioning

confidence: 99%

Rola ludzkich endogennych retrowirusów w patogenezie chorób autoimmunologicznych

et al. 2012

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SummaryThis paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants “vertically” by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

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Letter to the Editor

Cited by 7 publications

References 5 publications

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

Rola ludzkich endogennych retrowirusów w patogenezie chorób autoimmunologicznych

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