Tetramer monitoring can help to predict (recurrent) CMV reactivation and is a useful approach to monitor individual patients with increased risk for recurrent reactivation post HSCT; thus, it could help to identify patients in need of adoptive transfer of CMV-CTL or to optimize the use of antiviral drugs.
Seven patients with acute myeloid leukemia (AML) and two patients with chronic myelogenous leukemia (CML) were transplanted from HLA-identical sibling donors with CD34 þ cell-enriched stem cells (HSCTs) without further immunosuppression. The myeloablative standard transplantation protocol was adapted to include transfusion of gene-modified donor T cells after HSCT. Donor T cells were transduced with the replicationdeficient retrovirus SFCMM-3, which expresses herpes simplex thymidine kinase (HSV-Tk) and a truncated version of low-affinity nerve growth factor receptor (DLNGFR) for selection and characterization of transduced cells. Transduced T cells were detectable in all patients during follow-up for up to 5 years after transfusion. Proteomic screening for development of acute graft-versus-host disease (aGvHD) was applied to five of the seven patients with AML. No positivity for the aGvHD grade II-specific proteomic pattern was observed. Only one patient developed aGvHD grade I. To date, three of the patients with AML relapsed; one responded to three escalating transfusions of lymphocytes from the original donor and is in complete remission. Two were retransplanted with non-T cell-depleted peripheral blood stem cells from their original donors and died after retransplantation of septic complications or relapse, respectively. In one patient with CML, loss of bcr-abl gene expression was observed after an expansion of transduced cells. Seven of nine patients are alive and in complete remission.
Proteome analysis, the key technology for biomarker discovery, continues to gain importance in clinical diagnosis and follow-up. In this review we describe proteome analysis in the context of allogeneic, hematopoietic stem cell transplantation concentrating on capillary electrophoresis coupled on-line to mass spectrometry.
Background Newborn screening (NBS) has been shown to improve cystic
fibrosis (CF) disease course and has been widely implemented worldwide. This
monocentric study compared children diagnosed by NBS vs. a cohort preceding the
implementation of NBS in Germany in 2016 to evaluate ascribed benefits of
NBS.
Methods We compared all children with confirmed CF diagnosis
(n=19, “NBS group”) out of all children presenting with
positive NBS at our center after implementation of NBS (n=100) to
children diagnosed with CF at our center within 4 years before NBS
implementation (n=29, “pre-NBS group”) for outcomes of
anthropometry, gastrointestinal and pulmonary disease manifestations and
respiratory microbiology.
Results Children diagnosed by NBS had a lower incidence of initial
difficulty to thrive (15 vs. 41%) and showed higher mean z-scores for
Body-Mass-Index (BMI), weight and length at diagnosis and during study period.
Children in the pre-NBS group displayed higher proportions of oxygen-dependent
pulmonary exacerbations (10 vs. 0%). They show a significantly lower
amount of normal bacterial flora (p=0.005) along with a significantly
higher number of throat swab cultures positive for Pseudomonas aeruginosa
(p=0.0154) in the first year of life. Yet, pulmonary imaging did not
reveal less pulmonary morbidity in the NBS group.
Conclusions Our results confirm that NBS for CF leads to earlier diagnosis
and improves nutritional outcomes in early childhood. Although trajectories of
structural lung damage at early age were unaffected by NBS, NBS positive CF
patients at preschool age displayed less pulmonary exacerbations and
pathological bacteria in throat swabs.
CFTR encodes for a chloride and bicarbonate channel expressed at the apical membrane of polarized epithelial cells. Transepithelial sodium transport mediated by the amiloride-sensitive sodium channel ENaC is thought to contribute to the manifestation of CF disease. Thus, ENaC is a therapeutic target in CF and a valid cystic fibrosis modifier gene. We have characterized SCNN1B as a genetic modifier in the three independent patient cohorts of F508del-CFTR homozygotes. We could identify a regulatory element at SCNN1B to the genomic segment rs168748-rs2303153-rs4968000 by fine-mapping (Pbest = 0.0177), consistently observing the risk allele rs2303153-C and the contrasting benign allele rs2303153-G in all three patient cohorts. Furthermore, our results show that expression levels of SCNN1B are associated with rs2303153 genotype in intestinal epithelia (P = 0.003). Our data confirm that the well-established biological role of SCNN1B can be recognized by an association study on informative endophenotypes in the rare disease cystic fibrosis and calls attention to reproducible results in association studies obtained from small, albeit carefully characterized patient populations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.