Spontaneously-resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 patients, of which 144 episodes cleared spontaneously. Clearance of CMV DNAemia was significantly delayed in initial and recurrent self-resolving episodes featuring CMV DNA peak loads > 250 IU/mL compared with those displaying lower values. All-cause mortality in patients with self-resolving episodes of CMV DNAemia was comparable (P = 0.7) to that in patients with no CMV DNAemia and was not related to the CMV DNA peak load (≥250 IU/mL vs <250 IU/mL) (P = 0.6). In summary, in our setting, the magnitude of the CMV DNA peak load reached during self-resolving episodes of CMV DNAemia correlated directly with duration of episodes, but had no apparent impact on all-cause mortality taking patients with no documented CMV DNAemia as a reference.     

Identification of human parvovirus B19 among measles and rubella suspected patients from Cuba

Between September 2014 and December 2015, 298 sera from rash and fever patients from all over Cuba were investigated for specific IgM antibodies against measles, rubella, dengue, human parvovirus B19 (B19V) and human herpesvirus 6 (HHV6) using a commercial enzyme-linked immunosorbent assay kits. B19V IgM positive and equivocal samples were investigated by a polymerase chain reaction and genotyping. No measles, rubella or dengue cases were detected. HHV6-IgM antibodies were confirmed in 5.7% and B19V-IgM antibodies in 10.7% of the patients. A total of 31.3% of the B19V cases were between 5 and 9 years old and 34.4% were 20 years and older. The only B19V sequence obtained belonged to genotype 1a. Diagnosis was established for only 16% of the rash and fever patients, suggesting that other diseases such as Zika or Chikungunya may play a role.     

Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.