Genetic Basis of NK Cell Deficiency in 16 Patients with Inborn Errors of Immunity: Belarusian Single-Center Experience

Background and Aims Decreased NK cell numbers or impaired NK cell function are associated with increased susceptibility to viral infections, including HSV, CMV, EBV, and VZV. In children with inborn errors of immunity (IEI), viral infections are a frequent cause of severe complications and death. Methods This is a retrospective study of NK cell deficiency (%/absolute) in patients from Belarusian IEI registry over the past 10 years. Results We have found 16 patients (10 male and 6 female) with low (<5%, <100 cells/µl) NK cells. 13 are alive, one of them after HSCT; three patients died in early childhood from primary hemophagocytic lymphohistiocytosis (HLH). Most patients (58%) had mutations in genes associated with diseases of immune dysregulation PRF1, UNC13D (n = 2), SH2D1A (n = 2), XIAP, STAT3 GOF, FAS, AIRE, and NFAT5; predominantly antibody deficiency NFkB1, AICIDA, and also MYSM1, STAT3, PTPN6, and RUNX3. 6/16 had herpes viral infections, including CMV and EBV. Also, patients with low NK cell counts had clinical manifestations, such as anemia (n = 7), splenomegaly (n = 8), and lymphadenopathy (n = 3); infectious episodes in the form of bilateral pneumonia (n = 2), recurrent otitis (n = 1), and herpetic stomatitis (n = 1). Four patients had HLH. One of the patients developed Burkitt lymphoma; the other had juvenile arthritis since childhood. Conclusions In our cohorts, NK cell deficiency is more common in children with diseases of immune dysregulation.