BTK Inhibitors Impair Platelet-Mediated Antifungal Activity

In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cyto-kine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the re-lapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell im-pairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunother-apeutic approaches in these settings

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19 y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4 years, expression of vaccine interventions already adopted in some regions

Human parvovirus 4 'PARV4' remains elusive despite a decade of study

Human parvovirus 4 ('PARV4') is a small DNA tetraparvovirus, first reported in 2005. In some populations, PARV4 infection is uncommon, and evidence of exposure is found only in individuals with risk factors for parenteral infection who are infected with other blood-borne viruses. In other settings, seroprevalence studies suggest an endemic, age-associated transmission pattern, independent of any specific risk factors. The clinical impact of PARV4 infection remains uncertain, but reported disease associations include an influenza-like syndrome, encephalitis, acceleration of HIV disease, and foetal hydrops. In this review, we set out to report progress updates from the recent literature, focusing on the investigation of cohorts in different geographical settings, now including insights from Asia, the Middle East, and South America, and discussing whether attributes of viral or host populations underpin the striking differences in epidemiology. We review progress in understanding viral phylogeny and biology, approaches to diagnostics, and insights that might be gained from studies of closely related animal pathogens. Crucial questions about pathogenicity remain unanswered, but we highlight new evidence supporting a possible link between PARV4 and an encephalitis syndrome. The unequivocal evidence that PARV4 is endemic in certain populations should drive ongoing research efforts to understand risk factors and routes of transmission and to gain new insights into the impact of this virus on human health

First evidence of root morphological and architectural variations in young Posidonia oceanica plants colonizing different substrate typologies

Root morphology and root system architecture of young Posidonia oceanica plants established on two contrasting substrate types, sand and rock, were examined to provide insights into the strategy of adaptation of seagrasses to their environment. After germination, seedlings were planted on sandy patches and on rock within the same area, and survived plants were collected five years later for measurements of the size of the entire root complex and analysis of individual morphological and architectural root traits. Collected plants exhibited up to nine highly intermingled root systems and approx. 2.5 m of total root length. Maximum horizontal extension, total biomass and total length of roots were not significantly affected by substrate. However, on sand roots grew vertically reaching up to 13 cm, while on rock they extended more horizontally and did not penetrate deeper than 5-7 cm leading to the formation of a shallow, densely packed root complex. On rock, the number and the length of second-order laterals on an individual root system were reduced and the topological index higher than on sand (0.8 vs. 0.7) reflecting a more simple (herringbone) branching pattern. Again, root diameter was greater than on sand. The results suggest that P. oceanica can adjust root traits early during plant development according to substrate typology to maximize anchorage and substrate exploration efficiency. This plasticity enables the species to establish and persist also on rocky bottoms which generally prevent establishment of the majority of seagrasses

Plastics and sedimentation foster the spread of a non-native macroalga in seagrass meadows

Plastics are found in marine environments worldwide, and their effects on macrophytes (seagrasses and macroalgae) colonizing sandy bottoms are still poorly known. Seagrass meadows are valuable but declining ecosystems due to local and global-change related stressors, including sediment disturbance and introduced macroalgae. Understanding whether plastics pose a further threat to seagrasses is critically important. In two simultaneous additive experiments performed in an aquaculture tank, we examined the individual and combined effects of macroplastics (non-biodegradable high-density polyethylene and biodegradable starch-based) and sedimentation (no and repeated sedimentation) on the performance (in terms of biomass and architectural variables) of a native Mediterranean seagrass (Cymodocea nodosa) and an introduced macroalga (Caulerpa cylindracea), and on the intensity of their interactions. Macroplastics were still present in sediments after 18 months. Cymodocea nodosa produced a greater biomass and longer horizontal rhizome internodes forming clones with more spaced shoots probably to escape from plastics. Plastics prevented C. nodosa to react to sedimentation by increasing vertical rhizome growth. Under C. cylindracea invasion, C. nodosa allocated more biomass to roots, particularly to fine roots. In the presence of C. nodosa, C. cylindracea performance was reduced. High-density polyethylene (HDPE) plastic and sedimentation shifted species interactions from competitive to neutral. These results suggest that both HDPE and biodegradable starch-based macroplastics, if deposited on marine bottoms, could make seagrasses vulnerable to sedimentation and reduce plant cover within meadows. HDPE plastic and sedimentation could contribute to the decline of seagrass habitats by facilitating the spread of non-native macroalgae within meadows. Overall, the study highlights the urgent need to implement more effective post-marketing management actions to prevent a further entering of plastics in natural environments in the future, as well as to establish to conservation measures specifically tailored to protect seagrass habitats from plastic pollution