Immune system parameters in children of Central and Eastern Europe: the CESAR study

OBJECTIVE: of this paper is to compare observed values of immune parameters obtained in the CESAR study (The Central Europe Study of Air Pollution and Respiratory Health, funded by EC PHARE program) with ranges derived from other large population-based studies. STUDY DESIGN: Data were collected in healthy school children aged 9-11 years, in 6 countries: Bulgaria, the Czech Republic, Hungary, Poland, Romania and the Slovak Republic with the same standard approach in 1996. Random samples of 85 children per country, from 19 communities were selected from children having completed the health questionnaire, in total 495 children were analyzed. Lymphocyte subsets were determined by two-colour flow cytometric immunophenotyping using the lysed whole blood method (Becton-Dickinson). For determination of immunoglobulin concentration in sera nephelometric method (Behring Nephelometer system) was used. RESULTS: Medians, (5th-95th percentiles) of the lymphocyte subsets absolute count (x 10(9)/l) were as follows: CD19+ B cells 0.36 (0.13-0.66), total CD3+ T cells 1.74 (0.98-2.90), CD3+CD4+ helper-inducer T cells 0.95 (0.47-1.78), CD3+CD8+ suppressor/cytotoxic T cells 0.71 (0.38-1.22), CD3-CD16+56+ NK cells 0.36 (0.14-0.78), and for CD3+CD4+/CD3+CD8+ ratio 1.4 (0.8-2.4). Medians, (5th-95th percentiles) of percentages of lymphocyte subpopulations (%) were as follows: CD19+ B 13 (7-22), CD3+ T 70 (59-80), CD3+CD4+ T 38 (27-48), CD3+CD8+ T 28 (20-39), CD3-CD16+56+ NK cells 14 (6-27). Medians, (2.5th-97.5th percentiles) of the total immunoglobulin [g/l] were 11.7 (7.4-18.2) for IgG, 1.2 (0.5-2.5) for IgM, and 1.5 (0.5-3.4) for IgA. Based on the aspects of the size of the CESAR immune biomarker study and on the use of the standardized protocols we recommend to use the reference ranges on lymphocyte subsets and immunoglobulin in Europe as provided by this study

Clinical Assessment of Anti-Viral CD8+ T Cell Immune Monitoring Using QuantiFERON-CMV® Assay to Identify High Risk Allogeneic Hematopoietic Stem Cell Transplant Patients with CMV Infection Complications

The reconstitution of anti-viral cellular immunity following hematopoietic stem cell transplantation (HSCT) is crucial in preventing cytomegalovirus (CMV)-associated complications. Thus immunological monitoring has emerged as an important tool to better target pre-emptive anti-viral therapies. However, traditional laboratory-based assays are too cumbersome and complicated to implement in a clinical setting. Here we conducted a prospective study of a new whole blood assay (referred to as QuantiFERON-CMV®) to determine the clinical utility of measuring CMV-specific CD8+ T-cell responses as a prognostic tool. Forty-one evaluable allogeneic HSCT recipients underwent weekly immunological monitoring from day 21 post-transplant and of these 21 (51.2%) showed CMV reactivation and 29 (70.7%) developed acute graft-versus-host disease (GvHD). Patients with acute GvHD (grade≥2) within 6 weeks of transplant showed delayed reconstitution of CMV-specific T-cell immunity (p = 0.013) and a higher risk of CMV viremia (p = 0.026). The median time to stable CMV-specific immune reconstitution was 59 days and the incidence of CMV reactivation was lower in patients who developed this than those who did not (27% versus 65%; p = 0.031). Furthermore, a failure to reconstitute CMV-specific immunity soon after the onset of CMV viraemia was associated with higher peak viral loads (5685 copies/ml versus 875 copies/ml; p = 0.002). Hence, QuantiFERON-CMV® testing in the week following CMV viremia can be useful in identifying HSCT recipients at risk of complicated reactivation