Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up.

Oral Cladribine Impairs Intermediate, but Not Conventional, Monocyte Transmigration in Multiple Sclerosis Patients across a Model Blood-Brain Barrier.

Multiple sclerosis (MS) is a disease in which the immune system damages components of the central nervous system (CNS), leading to the destruction of myelin and the formation of demyelinating plaques. This often occurs in episodic "attacks" precipitated by the transmigration of leukocytes across the blood-brain barrier (BBB), and repeated episodes of demyelination lead to substantial losses of axons within and removed from plaques, ultimately leading to progressive neurological dysfunction. Within leukocyte populations, macrophages and T and B lymphocytes are the predominant effectors.

Circulating CCR6ILC proportions are lower in multiple sclerosis patients.

Objectives: The role of innate lymphoid cells (ILC), particularly helper ILC, in the pathogenesis of multiple sclerosis (MS) is not well understood. Here, we present a comprehensive analysis of peripheral ILC subsets in MS patients prior and after alemtuzumab administration using mass cytometry.

Methods: Circulating ILC were analysed by mass cytometry in MS patients before and after alemtuzumab.

A health sector response to the commercial determinants of health.

Aim: To develop and apply a theoretical framework to assess the rigour of a district health organisation's response to the commercial determinants of health (CDoH).

Methods: The multi-method study incorporated literature reviews of CDoH strategies and ways in which organisations can respond; policy document review; and 12 qualitative, semi-structured, key informant interviews.

Results: A theoretical framework was developed summarising CDoH and potential responses.

Mass cytometry reveals cladribine-induced resets among innate lymphoid cells in multiple sclerosis.

Here we present a comprehensive mass cytometry analysis of peripheral innate lymphoid cell (ILC) subsets in relapsing/remitting MS (RRMS) patients prior to and after onset of cladribine tablets (CladT). ILC analysis was conducted on CyTOF data from peripheral blood mononuclear cells (PBMC) of MS patients before, 2 and 6 months after onset of CladT, and non-MS controls. Dimensionality reduction was used for immunophenotyping ILC subsets.

Trans-Endothelial Migration of Memory T Cells Is Impaired in Alemtuzumab-Treated Multiple Sclerosis Patients.

The breakdown of the blood-brain barrier (BBB) and the trans-endothelial migration of lymphocytes are central events in the development of multiple sclerosis (MS). Autoreactive T cells are major players in MS pathogenesis, which are rapidly depleted following alemtuzumab treatment. This modulation, in turn, inhibits CNS inflammation, but alemtuzumab's effect on T cell migration into the CNS has been less studied.

Cladribine Reduces Trans-Endothelial Migration of Memory T Cells across an In Vitro Blood-Brain Barrier.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory effect on lymphocytes at the blood-brain barrier (BBB) in addition to its lymphocyte-depleting and modulating effects, this has not been properly studied.

Peripheral B-cell dysregulation is associated with relapse after long-term quiescence in patients with multiple sclerosis.

B cells play a major role in multiple sclerosis (MS), with many successful therapeutics capable of removing them from circulation. One such therapy, alemtuzumab, is thought to reset the immune system without the need for ongoing therapy in a proportion of patients. The exact cells contributing to disease pathogenesis and quiescence remain to be identified.

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM Cell Signature.

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls.

Permethrin-treated baby wraps for the prevention of malaria: results of a randomized controlled pilot study in rural Uganda.

Background: Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed.

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions.

Selective modulation of trans-endothelial migration of lymphocyte subsets in multiple sclerosis patients under fingolimod treatment.

Multiple sclerosis (MS) is an autoimmune disorder where auto-aggressive T cells target the central nervous system (CNS), causing demyelination. The trans-endothelial migration of leucocytes across the blood-brain barrier (BBB) is one of the earliest CNS events in MS pathogenesis. We examined the effect of the disease state and treatment with fingolimod on the transmigration of peripheral blood mononuclear cells (PBMCs) in an in vitro BBB model.

Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand.

IgG B cells are associated with the development of multiple sclerosis.

Objectives: Disease-modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG antibodies and their uncharacterised B-cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically.

The clinical profile of NMOSD in Australia and New Zealand.

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand.

Fatal reversible cerebral vasoconstriction syndrome.

We report four fatal cases of fulminant reversible cerebral vasoconstriction syndrome, all initially diagnosed as primary central nervous system vasculitis and treated with corticosteroids. Although reversible cerebral vasoconstriction syndrome is usually self-limiting without permanent neurologic deficits, rarely it can be fatal and worse outcomes have been associated with corticosteroid treatment.

Incidence and prevalence of NMOSD in Australia and New Zealand.

Objectives: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry.

Background: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established.

Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

Background: No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier.

Objectives And Methods: To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production.

Differential Toxicity of Antibodies to the Prion Protein.

Antibodies against the prion protein PrPC can antagonize prion replication and neuroinvasion, and therefore hold promise as possible therapeutics against prion diseases. However, the safety profile of such antibodies is controversial. It was originally reported that the monoclonal antibody D13 exhibits strong target-related toxicity, yet a subsequent study contradicted these findings.

Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells.

Autosomal dominant congenital spinal muscular atrophy is characterized by predominantly lower limb weakness and wasting, and congenital or early-onset contractures of the hip, knee and ankle. Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown. It has been hypothesized that differences in the timing and site of anterior horn cell loss in the central nervous system account for the variations in clinical phenotype between different forms of spinal muscular atrophy, but there has been a lack of neuropathological data to support this concept in dominant congenital spinal muscular atrophy.

Epitope-specific anti-prion antibodies upregulate apolipoprotein E and disrupt membrane cholesterol homeostasis.

The mechanisms of neuronal degeneration induced by the transformation of normal cellular prion protein (PrP(C)) into disease-associated PrP(Sc) are not fully understood. Previous reports have demonstrated that cross-linking cellular prion protein by anti-PrP(C) antibodies can promote neuronal apoptosis. In this report, we now show that treatment of neuronal cells with anti-prion antibodies leads to sequestration of free cholesterol in cell membranes, significant overexpression of apolipoprotein E, and to cytoplasmic phospholipase A2 activation as well as to production of prostaglandin.

Unswitched immunoglobulin M response prolongs mouse survival in prion disease.

Several studies have failed to demonstrate the presence of immune responses to infectious prions during the course of prion disease, reflecting the identical primary structure of normal and disease-associated isoforms and the widespread expression of the normal cellular form of prion protein, PrP(C), leading to B- and/or T-cell tolerance of disease-associated isoforms and also possibly because antigen-presenting cells are unable to process the highly aggregated, detergent-insoluble, protease-resistant form, PrP(Sc). Under certain circumstances, PrP(Sc) can be revealed to the immune system in immunogenic form, and it has been shown previously that anti-PrP antibodies can be induced to prions immunoadsorbed to Dynabeads using specific anti-PrP monoclonal antibodies, even in PrP-sufficient mice. This study demonstrated in a murine scrapie model that PrP-Dynabeads effectively stimulated the immune system to produce anti-PrP IgM antibodies over prolonged periods after repeated immunization.

Beta-PrP form of human prion protein stimulates production of monoclonal antibodies to epitope 91-110 that recognise native PrPSc.

Prion diseases are associated with accumulation of strain-dependent biochemically distinct, disease-related isoforms (PrP(Sc)) of host-encoded prion protein (PrP(C)). PrP(Sc) is characterised by increased beta-sheet content, detergent insolubility and protease resistance. Recombinant alpha-PrP adopts a PrP(C)-like conformation, while beta-PrP conformationally resembles PrP(Sc), to these we raised 81 monoclonal antibodies in Prnp(0/0) mice.