Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological dysfunction in the developing brain. This study analysed the different patterns of tissue damage, particularly in the ...brain, of fetuses with documented CMV infection. We studied 45 fetuses at 20-21 weeks of gestation with congenital CMV infection documented by invasive positive prenatal diagnosis. At the time of amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45 fetuses (29%). Histological and immunohistochemical characterization was performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The different degrees of brain damage were correlated with tissue viral load, inflammatory response, placental functionality, and extramedullary haematopoiesis. Even though a high CMV load was detected in all amniotic fluids, brain infection occurred in only 62% of the fetuses and with different degrees of severity. Tissues with a low viral load showed a globally weak inflammatory response, and fetuses had only mild brain damage, whereas tissues with a high CMV load showed prominent infiltration of the activated cytotoxic CD8+ T-lymphocytes responsible for immune-mediated damage. Furthermore, severe placental infection was associated with diffuse villitis and necrosis, consistent with functional impairment and possible consequent hypoxic cerebral damage. Brain injury induced by CMV congenital infection may be the result of uncontrolled viral replication, immune-mediated damage by cytotoxic CD8+ T-lymphocytes, and, in the presence of placental insufficiency, fetal hypoxia.
Background
In 28 pediatric allogeneic hematopoietic stem cell transplant (allo‐HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein–Barr virus (EBV) DNA monitoring on the ...development of EBV‐related post‐transplant lymphoproliferative disorder (EBV‐PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV‐PTLD.
Methods
Quantitative real‐time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV‐PTLD (≥10,000 copies/mL WB).
Results
High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched‐unrelated donor transplant, the reduced‐intensity conditioning regimen and, to a lesser extent, the in vivo T‐cell depletion with anti‐thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV‐PTLD.
Conclusion
WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo‐HSCT for the management of EBV infection and PTLD prevention.
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