Herpes simplex virus encephalitis: Intrathecal synthesis of oligoclonal virus-specific IgG, IgA and IgM antibodies

Journal of Neurology (Impact Factor: 3.38). 02/1982; 228(1):25-38. DOI: 10.1007/BF00313407
Source: PubMed


Paired specimens of serum and CSF from seven patients with acute herpes simplex virus encephalitis were examined during the acute illness or the convalescent stage or during both stages. Imprint immunofixation analyses of viral antibodies separated by agarose electrophoresis and by electrofocusing disclosed intrathecal production of herpes simplex virus IgG antibodies in all seven patients, and of IgA and IgM antibodies in six and three of six patients, respectively. Intrathecal production of herpes simplex virus-specific IgG and IgA was observed in two patients from whom samples were collected after 1 year, while intrathecal production of virus-specific IgM was not demonstrated later than 5 weeks after onset. The intrathecally synthesized IgG and IgM, and to a lesser extent IgA antibodies displayed oligoclonal characteristics. Oligoclonal bands of IgG were observed in the CSF of all patients. Evidence is presented to show that the bulk of the oligoclonal CSF IgG represents herpes simplex virus-specific antibodies. Intrathecally synthesized populations of herpes simplex virus antibodies cross-reacting with varicella-zoster virus were identified in three of the patients.

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    • "In a series of seven children having suffered from HSVE when they were younger, 3/5 who underwent lumbar puncture more than 8 years later had a partial or complete MRZ pattern but none did of those who underwent lumbar puncture in the same year (63). Moreover, IgG index increased over time, reaching a maximum at 1–2 months, then mostly remained elevated years later (63, 64). Systematic studies are lacking but in a single case of HSVE, an initially high AI for herpes subsequently abated whereas AI against multiple viruses (measles, parainfluenza, influenza, and adeno) increased (63). "
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    ABSTRACT: Although partly disease-irrelevant, intrathecal Ig synthesis is a typical feature of multiple sclerosis (MS) and is driven by the tertiary lymphoid organs (TLO). A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella and zoster viruses, which could also be involved in a wide range of pathogens. However, this non-specific synthesis is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain.We propose to explain the paradox of non-specific intrathecal synthesis by discussing the natural properties of TLO. In fact, besides local antigen-driven clonal expansion, circulating plasmablasts and plasma cells (PC) are non-specifically recruited from blood and gain access to survival niches in the inflammatory CNS. This mechanism, which has been described in other inflammatory disorders, takes place in the TLO. As a consequence, PCs recruited in brain mirror the individual’s history of immunization and intrathecal synthesis of IgG in MS may target a broad range of common infectious agents, a hypothesis in line with epidemiological data. Moreover, the immunization schedule and its timing may interfere with PC recruitment. If this hypothesis is correct, the reaction against EBV appears paradoxical: although early infection of MS patients is systematic, intrathecal synthesis is far lower than expected, suggesting a crucial interaction between MS onset and timing of EBV infection. A growing body of evidence suggests that the non-specific intrathecal synthesis observed in MS is also common in many chronic CNS inflammatory disorders. Assuming that cortical TLO in MS are associated with typical sub-pial lesions, we have coined the concept of ‘TLO-pathy’ to describe these lesions and take examples of them from non-MS disorders.
    Full-text · Article · Mar 2014 · Frontiers in Neurology
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    ABSTRACT: Alterations of cerebrospinal fluid (CFS) proteins and cells and blood-brain barrier impairment were determined in 4 patients with proven and 2 patients with presumptive herpes simplex virus encephalitis ( HSVE ) using simultaneous nephelometric measurements of CSF and serum albumin and immunoglobulins and combined MilliporeR filtration-cytocentrifuge cytologic techniques. The follow-up period ranged from 17 to 855 days. All patients showed intrathecal IgG synthesis which in 1 case continued for 28.5 months (855 days). The daily production of IgG in the central nervous system ranged up to 1157 mg. CSF-IgA and -IgM were also elevated in the early phase of the disease. The impairment of the blood-brain barrier was variable being apt to develop during the first 2 months of the disease and diminishing thereafter. Pleocytosis, mainly due to lymphoid cells, varied from slight to severe (325 X 10(3) cells/ml) and was observed in the CSF of all cases during the first 2 months. Lymphoid reaction (increase of enlarged stimulated lymphoid cells) was persistent and was the most pronounced cellular alteration. The lymphoid reaction and intrathecal IgG synthesis indicated continuous immunoactivation of the CNS, which was most intensive during the first 2 months and appeared to persist for at least 16-28.5 months.
    No preview · Article · Apr 1984 · Journal of the Neurological Sciences
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    ABSTRACT: A new method for detecting viral antibodies in cerebrospinal fluid is described. The technique has many advantages over previously published methods in that it is highly sensitive eliminating the need to concentrate the CSF, takes 5 h to complete, avoids the use of radionucleides, and most importantly circumvents problems associated with prozone effects which occur in immunoprecipitation reaction since the viral antigen is immobilized on nitrocellulose membranes.
    Full-text · Article · Jul 1984 · Bioscience Reports
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