A study of the prevalence of antibodies to Epstein-Barr virus in a large cohort of patients with early multiple sclerosis

Hintergrund: Die Multiple Sklerose (MS) ist eine entzündliche Erkrankung des zentralen Nervensystems (ZNS), die auf dem Boden einer Interaktion von genetischen und Umweltfaktoren entsteht. Der wichtigste und stärkste derzeit bekannte externe Risikofaktor für die Entwicklung einer MS ist eine Infektion mit dem Epstein-Barr-Virus (EBV). Frühere seroepidemiologische Untersuchungen haben übereinstimmend gezeigt, dass fast alle Patienten mit MS EBV-seropositiv sind. Sollte eine Infektion mit EBV tatsächlich eine Voraussetzung zur Entwicklung einer MS sein, wäre jedoch zu erwarten, dass Patienten mit MS ausnahmslos EBV-seropositiv sind. Somit stellt sich die Frage, ob es wirklich EBV-seronegative Patienten mit einer MS gibt. Zielsetzung: Zielsetzung der vorliegenden Arbeit war die Bestimmung der Seroprävalenz von Antikörpern gegen das EBV in einer großen Kohorte von Patienten mit früher MS. Methodik: In Serumproben von 901 Patienten mit einem klinisch isolierten Syndrom (KIS, der klinischen Erstmanifestation einer MS) oder schubförmiger MS aus der deutschen nationalen MS-Kohorte wurden IgG-Antikörper gegen das Epstein-Barr nukleäre Antigen-1 (EBNA-1) mit einem Chemilumineszenz-Immunoassay (CLIA) gemessen. Antikörper gegen das EBV viral capsid antigen (VCA) wurden bei EBNA-1-Antikörper-seronegativen Patienten ebenfalls mittels CLIA analysiert. EBNA-1- und VCA-Antikörper-seronegative Patienten wurden mit einem EBV-IgG-Immunoblot untersucht. Zur Ermittlung der EBV-Seroprävalenz in einer Kontrollpopulation wurde in einer großen Krankenhauspopulation (n=16.163) aus Berlin/Norddeutschland die EBV-Seroprävalenz in unterschiedlichen Altersgruppen von 80 Jahren ermittelt. Ergebnisse: Von 901 Patienten mit KIS/RRMS hatten 839 IgG-Antikörper gegen EBNA-1. IgG-Antikörper gegen VCA wurden bei 45 von 62 EBNA-1-Antikörper seronegativen Patienten nachgewiesen. Unter Verwendung von EBV-IgG-Immunoblots wurden bei allen übrigen 17 Patienten IgG-Antikörper gegen EBV gefunden. Somit waren alle 901 Patienten (100%) mit KIS/RRMS, die in unsere Studie eingeschlossen wurden, seropositiv für EBV. Die EBV-Seroprävalenz in der Krankenhauspopulation stieg mit zunehmendem Alter in allen 5-Jahres-Alterskohorten an, erreichte aber in keiner der untersuchten Altersgruppen 100%. Schlussfolgerungen: Die Abwesenheit von EBV-seronegativen Personen in dieser gut charakterisierten Kohorte von Patienten mit früher MS weist auf eine zentrale Rolle von EBV bei der MS hin. Eine negative EBV-Serologie bei Patienten mit Verdacht auf eine entzündliche Erkrankung des ZNS spricht gegen eine MS und sollte anderweitige Diagnosen in Betracht ziehen lassen.Background: Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system, which develops through an interaction of genetic and environmental factors. Epstein-Barr virus (EBV) is the most important and strongest currently known risk factor for MS. Previous seroepidemiological studies have consistently shown that almost all patients with MS are EBV-seropositive. However, if EBV infection was indeed a prerequisite for development of MS, one would expect that all patients with MS (100%) would be EBV seropositive. The question therefore arises whether EBV seronegative patients with MS do really exist. Objective: The present study aimed to determine the seroprevalence of antibodies against EBV in a large cohort of patients with early MS. Methods: In serum samples from 901 patients with a clinically isolated syndrome (CIS, the first clinical manifestation of multiple sclerosis) or with early relapsing-remitting MS (RRMS) from the German National MS cohort antibodies to Epstein-Barr nuclear antigen-1 (EBNA-1) were measured by a chemiluminescence immunoassay (CLIA). Antibodies to the EBV viral capsid antigen (VCA) were analyzed in EBNA-1 antibody seronegative patients by CLIA as well. EBV IgG immunoblot was used to analyze EBNA-1 and VCA antibody seronegative patients. To determine the EBV seroprevalence in a control population, we determined the EBV seroprevalence in different age groups ranging from 80 years in a large hospital population (n = 16,163) from Berlin/Northern Germany. Results: Of the 901 patients with CIS/RRMS, 839 had IgG antibodies to EBNA-1. IgG antibodies to VCA were detected in 45 of 62 EBNA-1 antibody seronegative patients. Using EBV IgG immunoblots, IgG antibodies to EBV were found among all the remaining 17 patients. Therefore, all 901 patients (100%) with CIS/RRMS included in our study were seropositive for EBV. EBV seropositivity increased with increasing age in the hospital population, but did not reach 100% in any of the examined age groups. Conclusions: The absence of EBV seronegativity in this well-characterized cohort of patients with early MS indicates a central role of EBV in MS. EBV seronegativity in patients with suspected inflammatory central nervous system diseases should alert clinicians to take into account diagnoses other than MS

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS

Multilayer Reading of the Urban Environment as a Method of Studying Space Transformation

Abstract: The urban environment is undergoing significant transformations driven by a multitude of factors, raising methodological questions about forecasting these changes within the context of sustainable development. This article delves into the multifaceted realm of urban science, exploring how it scrutinizes urban spaces, the tools it employs, and the aspects it often overlooks. Contemporary urban science confronts the intricate web of constituents that comprise a city system and their intricate interplay. This complexity underscores the fragmentary and non-comprehensive nature of modern urban studies. The questions of what urban science is, from what point of view and with what tools it examines the urban space, and which phenomena are ignored or incompletely studied in that process were studied. Based on the complexity level of the constituent elements of the city system and the interrelationship of these elements, the non-comprehensive and fragmentary character of studies of modern urban science has been formulated, and "Reading" the city becomes an essential endeavor, unveiling the city's narrative, culture, and identity. This article contemplates the principles and methodologies of reading the urban landscape, recognizing it as a dynamic, ever-evolving text that we must interpret and comprehend. Article states the need for "reading" the city and form the "language" of the city applying the concept of "textuality" as an interdisciplinary method to study the space, as well as the principles and methods of reading the urban landscape. The study employs a multidisciplinary approach, bringing together diverse methods to shed light on the multifaceted urban landscape. This holistic and interdisciplinary approach is vital in addressing the dynamic challenges and opportunities posed by modern urbanization. Keywords: urbanism, landscape, transformation, identity, textuality