Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients

Zivadinov, Robert; Nasuelli, Davide; Tommasi, Maria Antonietta; Serafin, Maurizia; Bratina, Alessio; Ukmar, Maja; Pirko, Istvan; Johnson, Aaron J.; Furlan, C.; Mucelli, Roberto Pozzi; Monti-Bragadin, Luisa; Grop, Attilio; Zambon, Massimo; Antonello, Rodolfo M.; Cazzato, Giuseppe; Zorzon, Marino

doi:10.1179/016164106x98134

Cited by 48 publications

(49 citation statements)

References 41 publications

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“…Other mechanisms could also be considered. A protective effect of CMV was previously reported in patients with multiple sclerosis (Zivadinov et al, 2006;Pirko et al, 2012). Although an autoimmune nature of schizophrenia has not been determined (Schattner et al, 1996;Goldsmith and Rogers, 2008), results of some studies are suggestive of the possibility that autoimmune components play a role in etiopathogenic pathways leading to schizophrenia, at least in some subgroups of subjects (Eaton et al, 2006;Goldsmith and Rogers, 2008;Eaton et al, 2010;Chen et al, 2012).…”

Section: Discussionmentioning

confidence: 72%

“…Although an autoimmune nature of schizophrenia has not been determined (Schattner et al, 1996;Goldsmith and Rogers, 2008), results of some studies are suggestive of the possibility that autoimmune components play a role in etiopathogenic pathways leading to schizophrenia, at least in some subgroups of subjects (Eaton et al, 2006;Goldsmith and Rogers, 2008;Eaton et al, 2010;Chen et al, 2012). Because CMV has an immunosuppressive effect (Rubin, 1989;Zivadinov et al, 2006;Varani et al, 2009), it might ameliorate the autoimmune damage and consequently decrease the likelihood of developing schizophrenia in vulnerable individuals with autoimmune reactions, which are potentially implicated in the etiopathophysiology of schizophrenia. Thus those who have the same vulnerabilities for developing schizophrenia and did not encounter CMV are potentially more prone to become cases.…”

Section: Discussionmentioning

confidence: 99%

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Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

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a b s t r a c t a r t i c l e i n f oIntroduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways. Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls. Results: Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR = 1.08, p = 0.06). Study participants with higher cytomegalovirus (CMV) IgG antibody levels had a reduced risk of developing schizophrenia (HR = 0.90; p = 0.02). While IgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia. Conclusion: Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious/food antigens might be an indicator of an altered immune response to antigenic stimuli.Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

View full text Add to dashboard Cite

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“…In work performed among paediatric subjects, there was also a higher percentage of positive cases, but with differences more accentuated than in adults [17][18][19]. The study performed by Zivadinov et al [43] was the only one in which the proportion of positive results was higher in controls than in cases. The study with the highest OR was published by Pohl et al [19] and that with highest weight was published by Bray et al [23], both of which indicate the existence of an association between the virus and the disease.…”

Section: Anti-vca Igg Determinationmentioning

confidence: 79%

“…To check for exposure to the virus, most authors employed the high predictive value methods (serology, molecular diagnosis), using the same test for cases and controls. Specifically, on the aspect of antibody study, articles of the highest quality were those by Zivadinov et al [43], Haahr et al [4], Myhr et al [34], Sundström et al [10] and Wandinger et al [42]. However, we may note the scarcity of comparison between cases and controls in the majority of the articles with molecular studies.…”

Section: Discussionmentioning

confidence: 99%

“…Individually considered, the studies with the highest quality were those by Myhr et al [34], which stated a significant association between EBV and MS, and those by Sundström et al [10] and Zivadinov et al [43], which did not find any significant association. After a meta-regression to understand the relationship between the quality of the study and the corresponding OR, the said relationship was found to be significant (p=0.017).…”

Section: Anti-vca Igg Determinationmentioning

confidence: 99%

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Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Santiago

Gutiérrez

Sorlózano

et al. 2010

Eur J Clin Microbiol Infect Dis

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Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of casecontrol observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using "Epstein-Barr virus" and "multiple sclerosis" as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR]=5.5; 95% confidence interval [CI]=3.37-8.81; p<0.0001), anti-complex EBNA IgG (OR=5.4; 95% CI= 2.94-9.76; p<0.0001) and anti-EBNA-1 IgG (OR=12.1; 95% CI=3. 13-46.89; p<0.0001). No significant association could be found when studying anti-EA IgG (OR=1.3; 95% CI=0.68-2.35; p=0.457), EBV DNA in serum (OR= 1.8; p=0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR=0.9; 95% CI=0.38-2.01; p=0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anticomplex EBNA and anti-VCA IgG.

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Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis

Perlejewski

Bukowska-Ośko

Nakamura

et al. 2016

Advances in Experimental Medicine and Biology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results.

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Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients

Cited by 48 publications

References 41 publications

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis

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