In patients with B-cell chronic lymphocytic leukemia (B-CLL), the absolute number of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n ؍ 12; Rai I-II, n ؍ 10; Rai III-IV, n ؍ 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses. In all Rai stages a significant increase in the absolute numbers of CD3 ؉ cells was observed. Whereas the number of CD4 ؉ cells was not different from controls, patients with B-CLL showed significantly increased relative and absolute numbers of CD8 ؉ cells, which exhibited a CD45RA ؉ CD27 ؊ cytotoxic phenotype. Analysis of specific immune responses with tetrameric cytomegalovirus (CMV)-peptide complexes showed that patients with B-CLL had significantly increased numbers of tetramerbinding CMV-specific CD8 ؉ T cells. The rise in the total number of CD8 ؉ cytotoxic T cells was evident only in CMV-seropositive B-CLL patients. Thus, our data suggest that in patients with B-CLL the composition of T cells is shifted toward a CD8 ؉ cytotoxic cell type in an effort to control infections with persistent viruses such as CMV. Moreover, they offer an explanation for the high incidence of CMV reactivation in CLL patients treated with T cell-depleting agents, such as the monoclonal antibody (mAb) alemtuzumab (Campath; ␣-CD52 mAb). Furthermore, because in CMV-seronegative patients no increase in cytotoxic CD8 ؉ T cells is found, our studies do not support the hypothesis that tumor-specific T cells account for T-cell expansion in B-CLL.
SummaryMannose-binding lectin (MBL) is a component of innate immunity and thus particularly important in neonates in whom adaptive immunity is not yet completely developed. Promoter polymorphisms and structural exon-1 mutations in the MBL2 gene cause reduced or deficient MBL plasma concentrations. The aim of our study was to determine the prevalence of MBL deficiency in neonates admitted to the neonatal intensive care unit (NICU). Eighty-five NICU patients (69 premature) were included in the study. We measured MBL concentrations in umbilical cord and neonatal blood within 24 h after birth by ELISA technique. MBL2 genotypes ( n = = = = 67) were determined by Taqman analysis. MBL concentrations were measured longitudinally during three weeks in 26 premature neonates. The association between pre-and intra-partum clinical data and MBL concentrations was investigated. At birth, 29 (42%) premature and six (38%) term neonates had MBL plasma concentrations ≤ ≤ ≤ ≤ 0·7 µ µ µ µ g/ml which was regarded as deficient. Twenty-one (38%) premature and four (36%) term neonates had variant MBL2 haplotypes, corresponding to exon-1 mutations and the LXPA haplotype. MBL concentrations increased over time in neonates with wild-type MBL2 haplotypes, but not in neonates with variant haplotypes. Low MBL plasma concentrations were related to lower gestational age and variant MBL2 haplotypes. Umbilical cord and neonatal MBL plasma concentrations appeared to be similar. In conclusion, almost half of our NICU patients, especially the premature ones, were MBLdeficient at birth. These infants may be at increased risk of neonatal infections. MBL concentration can reliably be measured in umbilical cord blood and it is positively correlated with gestational and postnatal age.
SummaryWe investigated whether deficiency of mannose-binding lectin (MBL), a component of innate immunity, is associated with neonatal pneumonia and sepsis during the first 72 h, i.e. early onset, and during the first month after birth. In 88 neonatal intensive care patients (71 premature), MBL2 genotype and MBL plasma levels at birth were determined prospectively by Taqman analysis and enzyme-linked immunosorbent assay, respectively. Thirty-five neonates (40%) had low, i.e. Յ 0·7 mg/ml, MBL plasma levels at birth. Median (interquartile range) MBL plasma levels in 32 no early-onset sepsis (EOS) cases, 44 possible EOS cases and 11 EOS cases were 1·57 (0·57-2·67) mg/ml, 1·05 (0·41-1·70) mg/ml and 0·20 (0·10-0·77) mg/ml, respectively (P < 0·01). During the first month, 28 neonates (32%) had no infection, 49 (55%) had suspected infection, five (6%) had pneumonia and six (7%) had culture-proven sepsis. Low MBL levels at birth were associated both with an increased risk of developing pneumonia (OR: 12·0; 95% CI: 1·1-126·1; P = 0·04) and culture-proven sepsis (OR: 15·0; 95% CI: 1·5-151·3; P = 0·02). These results were confirmed by genetic analysis of MBL deficiency. Low MBL levels at birth are associated with an increased risk of early-onset sepsis, culture-proven sepsis and pneumonia during the first month of life.
Background: Central venous access device (CVAD)-related complications are associated with high morbidity rates. This study was performed to underline the importance of CVAD-complication prevention and treatment. Methods: An audit of practice of CVAD-related complications in pediatric oncology patients receiving a CVAD between January 2015 and June 2017 was performed. CVADs included were totally implantable venous access ports (TIVAPs), Hickman-Broviac® (HB), nontunneled, and peripherally inserted CVADs. Results: A total of 201 children, with 307 CVADs, were analyzed. The incidence rates per 1000 CVAD-days for the most common complications were 1.66 for malfunctions, and 1.51 for central line-associated bloodstream infections (CLABSIs). Of all CVADs inserted, 37.1% were removed owing to complications, of which 45.6% were owing to CLABSIs. In 42% of the CLABSIs, the CLABSI could be successfully cured with systemic antibiotic treatment only. Of all included patients, 5.0% were admitted to the intensive care unit owing to CLABSI. The HB-CVAD compared to the TIVAP was a risk factor for CVAD-related complications, CLABSIs and dislocations in particular. Conclusions: The incidence of CVAD-related complications is high. Research on the prevention and treatment of CVAD-related complications in pediatric oncology patients should be a high priority for all health care professionals. Type of study: Prognosis study (retrospective).
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