Intravenous Immunoglobulins Suppress the Recurrences of Genital Herpes Simplex Virus: A Clinical and Immunological Study

Abstract

Effective treatment is not currently available for suppressing the recurrence of genital herpes simplex virus (HSV) infections. Since intravenous immunoglobulins (IVIG) proved useful against HSV in experimental models, we treated patients with very high frequency of HSV genital recurrences (more than 15 episodes per year) with IVIG (400 mg/Kg every fourth week). The control group was treated with intermittent oral acyclovir (800 mg twice a day for one week every month). Both groups were treated for six months and, then, patients were followed-up to further six months. Both IVIG and acyclovir were effective in reducing the frequency of HSV genital recurrences as compared to base-line. However, patients treated with IVIG had a more striking reduction in the frequency of recurrences as well as both a shorter mean duration and a minor severity of the lesions as compared to acyclovir-treated patients. Furthermore, we found a trend indicating IVIG as more effective in reducing the viral load. Since in IVIG-recipients we found a strong increase of peripheral blood lymphocytes with natural killer (NK) surface phenotype, we suggest that the clinical effectiveness of IVIG treatment is probably mediated via the expansion of NK cell populations. Our study indicates that the treatment with IVIG is an effective and safe tool for suppressing the recurrences of genital HSV infections.

Subtly Impaired Humoral Immunity Predisposes to Frequently Recurring Genital Herpes Simplex Virus Type 2 Infection and Herpetic Neuralgia

“…The associations of the G3m g ,G1m a/a(x) haplotype and low subclass concentrations with frequent outbreaks of genital herpes raise the question: are IgG1 and IgG3 antibodies directed against some unknown epitope on HSV functionally active in early protection from symptomatic recurrences? In support of this, intravenous immunoglobulin treatment suppresses genital herpes recurrences in humans [33]. In mouse models, HSV-specific local IgG is important in protection against genital herpes [4].…”

Therapeutic Use of Immunoglobulins

“…Masci and colleagues [71] used IVIG to prevent recurrent genital HSV infection with suggestive benefit. The value of HSV monoclonal antibody or IVIG is being evaluated for treatment of disseminated neonatal disease.…”

Disseminated HSV-2 presenting with relapsing encephalomyelitis

“…IVIG therapy has been associated with a striking reduction in the frequency of recurrences, duration, and severity of genital HSV infections as compared to acyclovir alone, thought to be mediated by expansion of NK cell populations. 6 Once disseminated into the nervous system, HSV can have a secondary immune-mediated, relapsing course, which has been shown in a recent case series with patients additionally demonstrating NMDA receptor (NMDAR) and other synaptic protein antibodies. 7 Relapses can occur even after the CSF PCR seroconverts to negative, and they respond well to immunotherapy, as did our case.…”