Introduction and objective: Exchange transfusion (ET) is an important treatment method of newborns with hemolytic disease of the fetus and newborn (HDFN). One of the possible adverse effects of transfusion is transfusion-related immunomodulation (TRIM), which can through still unexplained mediators and mechanisms lead to a number of positive and negative clinical outcomes and affects the subsequent morbidity of blood recipients. The objective of the study is to investigate the impact of ET in the neonatal period on immune response and morbidity and to determine whether ET triggers TRIM.
Methods: The first part of the study is a prospective cohort analysis of the cellular immune response of 86 subjects. Thirty children of the experimental group received ET due to HDFN at the age of a few days and 56 healthy children in the control group did not receive any blood component. Blood concentrations of leukocytes, lymphocytes, lymphocyte populations and serum concentrations of inflammatory and regulatory cytokines were determined in all children at the age of six weeks and 13 months. The second part of the study is a retrospective cohort analysis of the specific humoral immune response to toxoid diphtheria and tetanus vaccine, serum autoantibodies and the incidence of bacterial and viral infections, allergic, autoimmune and cancer diseases of 74 subjects. Forty-one children of the experimental group received ET due to HDFN at the age of a few days and 33 healthy children in the control group did not receive any blood component.
Results and discussion: At the age of six weeks ET recipients presented with signs of immune exhaustion as they had significantly lower blood concentrations of activated monocytes, activated helper T cells, regulatory helper T cells, naive and transitional B lymphocytes compared to healthy infants. Thirteen months after ET immune exhaustion disappeared as the difference in the concentration of these cells was no longer present, but the difference between ET recipients and healthy children remained as ET recipients exhibited reduced variability of immune cells and cytokines concentration. After four doses of diphtheria and tetanus toxoid vaccine ET recipients showed effective and significantly better humoral immune response to diphtheria toxoid. ET recipients were more likely to develop varicella zoster virus infection; however, the incidence of other viral and bacterial infections, allergic, autoimmune, cancerous diseases and serum autoantibodies did not differ from healthy children.
Conclusions: ET in the neonatal period triggers TRIM as it affects specific cellular and humoral immune response. It causes short-term and transient immune exhaustion that resolves by 13 months of age. It improves the long-term humoral immune response to diphtheria toxoid vaccine and affects the incidence of varicella zoster virus infection. A possible mechanism of TRIM development could be a massive antigenic load, which in short term causes transient immune exhaustion and in long term an accelerated but less attuned maturation of the immune system. The humoral immune response to diphtheria and tetanus toxoid vaccine in ET recipients is at least comparable to the efficacy of the vaccine in healthy children, so ET recipients should be vaccinated with these two vaccines according to the official immunization schedule for healthy children.