Indeterminate measurable residual disease by multiparameter flow cytometry is associated with an intermediate risk of clinical relapse in adult patients with acute leukaemia.

Measurable residual disease (MRD) is useful for prognostication and for monitoring response to treatment in patients with acute leukaemia. MRD by multiparametric flow cytometry (MFC-MRD) utilises the leukaemia-associated immunophenotype (LAIP) and difference from normal (DfN) strategies to identify the leukaemic clone. Difficulties arise when the LAIP overlaps with normal regeneration, there is clonal evolution, or when the abnormal clone population is exceptionally small e.

Measurable Residual Disease (MRD) by Flow Cytometry in Adult B-Acute Lymphoblastic Leukaemia (B-ALL) and Acute Myeloid Leukaemia (AML): Correlation with Molecular MRD Testing and Clinical Outcome at One Year.

Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD study, one of the largest in Australia to date, we examined consecutive bone marrow aspirates from adult participants with B-ALL ( = 47) and AML ( = 87) sent for FC-MRD testing at a quaternary referral hospital in Sydney. FC-MRD results were correlated to corresponding Mol-MRD testing where available and clinical outcomes at three-month intervals over 1 year.

Murine Skin-resident γδT Cells Impair the Immune Response to HSV in Skin.

Background: HSV is an important cause of brain infection. Virus entry is often through breeches in the skin. γδT cells play an immunoprotective role in mice after corneal, genital or footpad (subcutaneous) HSV infection.

Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New South Wales, Australia.

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is a major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of the genetic diversity of RSV in Australia, nor the factors that shape this diversity.

Congenital Cytomegalovirus among Children with Cerebral Palsy.

Objectives: To determine the proportion of children with cerebral palsy (CP) and cytomegalovirus (CMV) DNA detected retrospectively in their newborn screening cards (NBSC), to compare the proportion of children with CMV DNA in their NBSC across spastic subtypes of CP, and to compare the sex and other characteristics of children with CP and CMV detected on their NSBC with those in whom CMV DNA was not detected.

Study Design: Retrospective observational study. Data were extracted from patient records on children with CP (birth years 1996-2014) from 2 Australian state CP registers and state-wide paediatric rehabilitation services with consent.

The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons.

Unlabelled: The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1.

Treg depletion attenuates the severity of skin disease from ganglionic spread after HSV-2 flank infection.

Regulatory T cells (Tregs) attenuate lesion severity and disease after HSV ocular or genital infection, but their role in cutaneous infection remains unclear. Treg depletion (anti-CD25 mAb in C57BL/6 mice or diphtheria toxin (DT) in DEREG mice) prior to tk-deficient HSV-2 flank infection significantly decreased skin lesion severity, granulocyte receptor-1(Gr-1(+)) cell number, and chemokine (KC) expression in the secondary skin, but significantly increased immune effectors and chemokine expression (MCP-1, KC, VEGF-A) in the draining LN, and activated, interferon-γ producing CD8(+)T cells in the ganglia. Treg depletion also significantly reduced HSV-2 DNA in the ganglia.

Herpes simplex virus infects skin gamma delta T cells before Langerhans cells and impedes migration of infected Langerhans cells by inducing apoptosis and blocking E-cadherin downregulation.

The role individual skin dendritic cell (DC) subsets play in the immune response to HSV remains unclear. We investigated the effect of HSV on DC virus uptake, viability, and migration after cutaneous infection in vitro and in vivo. HSV increased the emigration of skin DCs from whole skin explants over 3 d postinfection (p.

T regulatory cells contribute to the attenuated primary CD8+ and CD4+ T cell responses to herpes simplex virus type 2 in neonatal mice.

The first weeks of life are characterized by immune tolerance and increased susceptibility to intracellular pathogens. The neonatal adaptive response to HSV is attenuated compared with adult control models in humans and mice. T Regulatory cells (Tregs) control autoimmunity and excessive immune responses to infection.

Neonatal CD8+ T cells are slow to develop into lytic effectors after HSV infection in vivo.

HSV is an important neonatal pathogen. We defined the kinetics of the primary CTL response to HSV-2 in vivo in neonatal mice. Using a replication-defective HSV-2 virus, we demonstrate that neonates mount a primary HSV-specific CTL effector response in the draining LN, with delayed onset and shortened peak activity, in contrast to the rapid, strong response observed in adult mice.