The composition of MDSC-subpopulations PMN-like, M-like, and e-like MDSC is associated with the severity of infectious mononucleosis in pediatric patients

Background Primary infection with the Epstein-Barr virus (EBV) in early childhood is often asymptomatic, whereas infection with EBV during adolescence or adulthood may lead to infectious mononucleosis (IM). Sometimes severe complications like hepatitis, spleen rupture, or myocarditis may appear during IM. Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of regulatory immune cells with immunosuppressive activities. However, not much is known about the role of MDSC in IM. We assessed a clinical translational prospective study to examine the role of MDSC during the early and late phases of IM in pediatric patients. Method We performed a longitudinal analysis of PMN-like, M-like, and e-like MDSC frequencies in 37 pediatric patients during the early (V1 < 28 days after symptom onset (T onset ), V2 four to six weeks after T onset ) and late phases (V3 = six to 12 months after T onset ) of IM using flow cytometry-based analyses. In addition, we determined the correlation of frequencies of MDSC-like subpopulations with the complexity and severity of laboratory, clinical, and virological IM features. Results We detected comparable frequencies of total MDSC-like cells during the course of IM (V1 median: 22.87%, V2 median: 16.10%, and V3 median: 16.58% of CD33+ cells, respectively). However, we observed temporal dynamics of the MDSC-like subpopulations PMN-like, M-like, and e-like MDSC during the early and late phases of IM. The frequency of PMN-like MDSC decreased significantly from V1 to V2 ( P < 0.001 ) and from V1 to V3 ( P < 0.001 ). In contrast, the frequency of M-like MDSC decreased significantly from V1 to V2 ( P = 0.015) and increased from V2 to V3 ( P < 0.001). e-like MDSC frequencies increased significantly from V1 to V3 ( P < 0.001). We observed an increase in the proportion of PMN-like MDSC with the IM-complexity and severity laboratory score and ferritin levels. Conclusion Our data highlights the rationale for in-depth analyses of MDSC subpopulations in further studies on IM and contributes to obtaining a more differentiated picture of the ongoing changes in MDSC-like cell distribution and the relationship between frequencies of MDSC-like cells and the complexity and severity of laboratory, clinical, and virological IM features.