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Mikko Seppänen, Seppo Meri, Irma-Leena Notkola, Ilkka J. T. Seppälä, Eija Hiltunen-Back, Heikki Sarvas, Maija Lappalainen, Hannamari Välimaa, Anil Palikhe, Ville V. Valtonen, Marja-Liisa Lokki, Subtly Impaired Humoral Immunity Predisposes to Frequently Recurring Genital Herpes Simplex Virus Type 2 Infection and Herpetic Neuralgia, The Journal of Infectious Diseases, Volume 194, Issue 5, 1 September 2006, Pages 571–578, https://doi.org/10.1086/506477
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Abstract
BackgroundImmunogenetic factors predisposing to recurrent genital herpes remain poorly characterized
MethodsIn a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)–seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti–HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed
ResultsThe G3mg,G1ma/a(x) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0–12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7–7.8]; P=.001), but not of anti–HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06–0.81]; P=.022)
ConclusionsLow levels of antibody-dependent cellular cytotoxicity–mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation
- polymerase chain reaction
- simplexvirus
- inflammation
- genital herpes
- glycoproteins
- antibody-dependent cell cytotoxicity
- complement system proteins
- disease outbreaks
- epitopes
- haplotypes
- human herpesvirus 2
- hla-a antigens
- hla-a2 antigen
- immunogenetics
- immunophenotyping
- neuralgia
- immunoglobulins
- immunoglobulin g
- infections
- antibodies
- viruses
- recurrent genital herpes
- immunity, humoral
- genotype determination