We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 ...infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein of SARS-CoV-2. We analyzed participants with PCR-confirmed infection who had strong antibody responses (ratio >3) as positive controls and participants without symptoms of SARS-CoV-2 infection and without household contact with infected patients as negative controls. Using interferon-γ ELISpot, we observed that 78% of PCR-positive volunteers with undetectable antibodies showed T cell immunity against SARS-CoV-2. We observed a similar frequency (80%) of T-cell immunity in convalescent donors with strong antibody responses but did not detect immunity in negative controls. We concluded that, in convalescent patients with undetectable SARS-CoV-2 IgG, immunity may be mediated through T cells.
Salinomycin is a polyether antibiotic isolated from
Streptomyces albus that acts in different biological membranes as a ionophore with a preference for potassium. It is widely used as an ...anticoccidial drug in poultry and is fed to ruminants to improve nutrient absorption and feed efficiency. Salinomycin has recently been shown to selectively deplete human breast cancer stem cells from tumorspheres and to inhibit breast cancer growth and metastasis in mice. We show here that salinomycin induces massive apoptosis in human cancer cells of different origin, but not in normal cells such as human T lymphocytes. Moreover, salinomycin is able to induce apoptosis in cancer cells that exhibit resistance to apoptosis and anticancer agents by overexpression of Bcl-2, P-glycoprotein or 26S proteasomes with enhanced proteolytic activity. Salinomycin activates a distinct apoptotic pathway that is not accompanied by cell cycle arrest and that is independent of tumor suppressor protein p53, caspase activation, the CD95/CD95L system and the proteasome. Thus, salinomycin should be considered as a novel and effective anticancer agent that overcomes multiple mechanisms of apoptosis resistance in human cancer cells.
The role of HLA amino acid (AA) polymorphism for the outcome of hematopoietic cell transplantation (HCT) is controversial, in particular for HLA class II. Here, we investigated this question in ...nonpermissive HLA-DPB1 T-cell epitope (TCE) mismatches reflected by numerical functional distance (FD) scores, assignable to all HLA-DPB1 alleles based on the combined impact of 12 polymorphic AAs. We calculated the difference in FD scores (ΔFD) of mismatched HLA-DPB1 alleles in patients and their 10/10 HLA-matched unrelated donors of 379 HCTs performed at our center for acute leukemia or myelodysplastic syndrome. Receiver-operator curve-based stratification into 2 ΔFD subgroups showed a significantly higher percentage of nonpermissive TCE mismatches for ΔFD >2.665, compared with ΔFD ≤2.665 (88% vs 25%, P < .0001). In multivariate analysis, ΔFD >2.665 was significantly associated with overall survival (hazard ratio HR, 1.40; 95% confidence interval CI, 1.05-1.87; P < .021) and event-free survival (HR, 1.39; 95% CI, 1.05-1.82; P < .021), compared with ΔFD ≤2.665. These associations were stronger than those observed for TCE mismatches. There was a marked but not statistically significant increase in the hazards of relapse and nonrelapse mortality in the high ΔFD subgroup, whereas no differences were observed for acute and chronic graft-versus-host disease. Seven nonconservative AA substitutions in peptide-binding positions had a significantly stronger impact on ΔFD compared with 5 others (P = .0025), demonstrating qualitative differences in the relative impact of AA polymorphism in HLA-DPB1. The novel concept of ΔFD sheds new light onto nonpermissive HLA-DPB1 mismatches in unrelated HCT.
•Nonpermissive mismatches associated with survival after HCT reflect FD between recipient-donor HLA-DPB1.•FD within HLA-DPB1 is determined by the combined impact of nonconservative peptide-binding AA substitutions.
The importance of donor-specific antibodies (DSA) after liver transplantation (LT) for graft and patient survival is an ongoing controversy. So far it has not been elucidated when and in how far DSA ...are harmful for graft and patient survival. Therefore, we had the aim to investigate the association of DSA with complications after LT.
Data of 430 LT recipients were collected and statistically analyzed. Detection of HLA antibodies (Ab) was performed by Luminex assay.
DSA were detected in 81 patients (18.8%). These were mainly HLA class II Ab (81.5%). HLA class II Ab show a higher MFI (median: 5.300) compared to HLA class I Ab (median: 2.300). There is no association between MFI levels and development of complications after LT. However, cirrhosis occurred significantly more often in DSA positive patients (18%) than in patients without detectable DSA (9%, P = 0.027). All DSA positive patients with cirrhosis of the graft showed HLA class II antibodies (OR: 3.028; 95% CI: 1.51-6.075; P = 0.002).
Occurrence of HLA class II DSA after LT is associated with graft cirrhosis and may indicate a higher risk to develop graft damage independent on MFI and requires an individualized risk management.
Highlights • Added sensitivity of qPCR compared to STR chimerism post-SCT has clinical utility • Engraftment kinetics are imprinted by CMV serostatus and reactivation • Relapse prediction at a ...molecular state post-SCT is feasible by qPCR on PB • Chimerism conversion in response to DLI is protracted over several months • qPCR chimerism early post-transplant is more specific on PB than on BM
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