Therapy of chronic herpesvirus infection in frequently ill children. Possible causes of inefficiency

Abstract

A.S. Levina1,2, I.V. Babachenko1,2, N.V. Skripchenko1,2, T.A. Chebotareva3, O.I. Demina3 1St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation 2Children’s Scientific Clinical Center of Infectious Diseases of the Federal Medical Biological Agency of Russia, St. Petersburg, Russian Federation 3Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation Background: therapy for frequently ill children (FIC) with chronic herpesvirus infection includes antivirals and immunomodulators as these patients are considered immunocompromised. According to our data based on the prevalence of diseases and the viral replication activity, therapy may fail in 22% of cases. Aim: to identify a spectrum of rare genetic variants associated with primary immunodeficiency (PID) detected in FIC with stable, active persistence of herpesvirus infections that were resistant to repeat courses of antiviral and immunotropic therapy. Patients and Methods: DNA samples of 33 frequently ill children with chronic herpesvirus infection who did not respond to therapy were analyzed using targeted high-throughput multigene sequencing to identify mutations in PID-associated genes. Results: pathogenic variants matching the potential diagnosis of PID were identified in two (6.1%) children. Rare genetic variants associated with the development of autoinflammatory diseases were found in 54.5% of cases. The p.Gln705Lys NLRP3 gene variant was the most common finding — it was detected in 5 (15.2%) children. Rare variants of the MEFV gene (MEFV p.Thr767Ile and MEFV p.Lys695Arg) were found in three (9.2%) children. In seven (21.2%) children rare variants of the NOD2 gene were identified, in four of them (12.2%) it was NOD2 p.Leu1007fs. Conclusions: the inefficiency of therapy in frequently ill children with chronic herpesvirus infection could be associated with characteristics of the innate immune system. Such children should be referred to immunology consultant and undergo molecular genetic testing. The detection of rare genetic variants associated with autoinflammatory diseases in more than half of the patients indicates that frequent (occurring every month) diseases with fever may mimic hidden or sometimes typical autoinflammatory diseases, despite the detection of the markers of viral and bacterial agents in a child. Keywords: frequently ill children, chronic herpesvirus infection, rare genetic variants, primary immunodeficiency. For citation: Levina A.S., Babachenko I.V., Skripchenko N.V. et al. Therapy of chronic herpesvirus infection in frequently ill children. Possible causes of inefficiency. Russian Journal of Woman and Child Health. 2022;5(4):332–339 (in Russ.). DOI: 10.32364/2618-8430-2022-5-4-332-339.