Interferonopathies in atypical chronic active herpesvirus infections: a treatment strategy for interferon deficiency

A cytokine imbalance and interferonopathies associated with deficits of type I and type II interferons (IFN) are often observed in atypical chronic active herpesvirus infections (ACA-HVI). Objective. To study the features of IFN system functioning and cytokine profile in patients with ACA-HVI before and after the immune system correction integrative program (ISCIP) including local and systemic interferon therapy. Patients and methods. A total of 39 male and female patients aged 23–70 years with ACA-HVI characterized by isolated disorders in the IFN system were examined. The study included the following methods for herpesvirus detection: serodiagnostics and a real-time polymerase chain reaction (RT-PCR). The cytokine profile (interleukins IL-1β, IL1Ra, IL-6, IL-17) and the IFN system were analyzed by an enzyme-linked immunosorbent assay (ELISA). The study was approved by the Ethics Committee, and an informed consent was obtained from all patients. Results. Patients with ACA-HVI had antiviral immune response disorders. Against the background of serum IFN deficiency, induced and spontaneous production of IFNα and IFNγ, a functional impairment of cytokine profile with predominant hyper-production of proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor-α were revealed. Positive clinical and immunological effects of ISCIP were demonstrated. It was shown that IL1Ra can be used as a diagnostic biomarker to monitor the course and outcome of ACA-HVI. Conclusions. The developed ISCIP with the inclusion of targeted local and systemic interferon therapy for patients with ACA-HVI demonstrated high clinical and immunological efficacy against the background of the confirmed absence of anti-IFNα autoantibodies. © 2023, Dynasty Publishing House. All rights reserved.