Analysis of Candidate-Host Immunogenetic Determinants in Herpes Simplex Virus-Associated Mollaret's Meningitis


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Abstract

Infection due to herpes simplex virus (HSV) is associated with recurrent aseptic meningitis (Mollaret's meningitis); however, the neuropathogenesis of this disease remains unknown. We collected 20 cerebrospinal fluid (CSF) specimens that were positive for HSV DNA by using polymerase chain reaction (PCR) assay from patients with a clinical diagnosis of Mollaret's meningitis. Patients were predominantly female (female:male, 22:1), with an average age of 32.8 years (range, 18-46 years). Using direct sequence analysis of HSV PCR products obtained from the CSF, we determined that all of the patients were infected with HSV type 2. In addition, we evaluated polymorphisms in 2 human genomic loci, which are associated with either severe or recurrent microbial infections (interferon-γ receptor [IFN-γR] and mannose binding lectin [MBL]); these host genes were also amplified directly from the CSF specimens. No mutations were found in exons 2 or 3 of the IFN-γR gene (n=20). In contrast, there were 4 (20%), 4 (20%), and 0 mutations found in codons 52, 54, and 57, respectively, in exon 1 of MBL (n=20). A significantly higher frequency of codon 52 mutations (P=.04) was observed, compared with racially matched control patients.

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