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Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.
Med Hypotheses 2016; 91:109-113MH

Abstract

Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our hypothesis would link EBV infection, the most important environmental risk factor for MS, with intrathecal IgG synthesis, the most characteristic laboratory feature of MS. Besides explaining the origin of intrathecal IgG synthesis in patients with MS, the hypothesis could thus also provide a conceptual framework for clarifying the mechanism through which EBV contributes to the development of MS.

Authors+Show Affiliations

St. Josefs-Krankenhaus Potsdam, Potsdam, Germany. Electronic address: otto_carolin@yahoo.de.Institute of Virology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Labor Berlin, Charité-Vivantes GmbH, Berlin, Germany. Electronic address: joerg.hofmann@charite.de.Department of Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address: klemens.ruprecht@charite.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27142157

Citation

Otto, Carolin, et al. "Antibody Producing B Lineage Cells Invade the Central Nervous System Predominantly at the Time of and Triggered By Acute Epstein-Barr Virus Infection: a Hypothesis On the Origin of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis." Medical Hypotheses, vol. 91, 2016, pp. 109-113.
Otto C, Hofmann J, Ruprecht K. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis. Med Hypotheses. 2016;91:109-113.
Otto, C., Hofmann, J., & Ruprecht, K. (2016). Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis. Medical Hypotheses, 91, pp. 109-113. doi:10.1016/j.mehy.2016.04.025.
Otto C, Hofmann J, Ruprecht K. Antibody Producing B Lineage Cells Invade the Central Nervous System Predominantly at the Time of and Triggered By Acute Epstein-Barr Virus Infection: a Hypothesis On the Origin of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis. Med Hypotheses. 2016;91:109-113. PubMed PMID: 27142157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis. AU - Otto,Carolin, AU - Hofmann,Jörg, AU - Ruprecht,Klemens, Y1 - 2016/04/16/ PY - 2016/02/14/received PY - 2016/04/13/accepted PY - 2016/5/5/entrez PY - 2016/5/5/pubmed PY - 2017/6/16/medline KW - Antibodies KW - Antibody index KW - Cerebrospinal fluid KW - Epstein–Barr virus KW - Measles virus KW - Multiple sclerosis KW - Rubella virus KW - Serum KW - Varicella zoster virus SP - 109 EP - 113 JF - Medical hypotheses JO - Med. Hypotheses VL - 91 N2 - Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our hypothesis would link EBV infection, the most important environmental risk factor for MS, with intrathecal IgG synthesis, the most characteristic laboratory feature of MS. Besides explaining the origin of intrathecal IgG synthesis in patients with MS, the hypothesis could thus also provide a conceptual framework for clarifying the mechanism through which EBV contributes to the development of MS. SN - 1532-2777 UR - https://www.unboundmedicine.com/medline/citation/27142157/Antibody_producing_B_lineage_cells_invade_the_central_nervous_system_predominantly_at_the_time_of_and_triggered_by_acute_Epstein_Barr_virus_infection:_A_hypothesis_on_the_origin_of_intrathecal_immunoglobulin_synthesis_in_multiple_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(16)30040-8 DB - PRIME DP - Unbound Medicine ER -