Cerebrospinal fluid biomarkers as predictors of multiple sclerosis severity.

Background: Prognostic biomarkers at multiple sclerosis (MS) onset to predict disease severity may help guide initial therapy selection for people with MS. Over 20 disease-modifying treatments (DMTs) of varying levels of risk and efficacy now exist. The ability to predict MS severity would help to identify those patients at higher risk where a highly effective, but potentially risky, therapy would be optimal.

Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.

Background: Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures.

Growth differentiation factor 15 (GDF15) elevation in children with newly diagnosed cancer.

Background: Growth differentiation factor 15 (GDF15), an inflammatory marker and mediator of adult cancer cachexia, remains largely unexplored in children. GDF15 increases nausea, vomiting, and anorexia in cancer and contributes to malnutrition, with the potential to be a cachexia therapeutic target. No studies have examined GDF15 in children with newly diagnosed cancer.

Opportunities to implement manureshed management in the Iowa, North Carolina, and Pennsylvania swine industry.

The U.S. swine industry is diverse, but opportunities exist to strategically improve manure management, especially given much of the industry's vertical integration.

Alterations of host-gut microbiome interactions in multiple sclerosis.

Background: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder.

Alterations of the gut mycobiome in patients with MS.

Background: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied.

Methods: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months.

African Americans Have Differences in CSF Soluble TREM2 and Associated Genetic Variants.

Objective: To evaluate for racial differences in triggering receptor expressed on myeloid cells 2 (TREM2), a key immune mediator in Alzheimer disease, the levels of CSF soluble TREM2 (sTREM2), and the frequency of associated genetic variants were compared in groups of individuals who self-reported their race as African American (AA) or non-Hispanic White (NHW).

Methods: Community-dwelling older research participants underwent measurement of CSF sTREM2 concentrations and genetic analyses.

Results: The primary cohort included 91 AAs and 868 NHWs.

TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for the clearance of myelin debris in areas of demyelination, a key step to allow remyelination. TREM2 is expressed by microglia and promotes microglial survival, proliferation, and phagocytic activity.

The gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk.

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been associated with Alzheimer's disease (AD). TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may reveal new pathological mechanisms and lead to the identification of therapeutic targets.

Predicting optimal response to B-cell depletion with rituximab in multiple sclerosis using CXCL13 index, magnetic resonance imaging and clinical measures.

Background: B-cell depleting drugs show promise for treating multiple sclerosis.

Objective: We sought predictors of optimal response to rituximab, a B-cell depleting antibody, to help guide therapy selection.

Methods: We performed a post hoc study of 30 relapsing multiple sclerosis patients with breakthrough disease while on beta-interferon or glatiramer acetate who were treated with add-on rituximab.

B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.

B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part as a result of the success of B cell-depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B cell Ag presentation was suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support Ag-specific autoimmune responses by CD4 T cells in EAE is lacking.

TREM2 regulates microglial cell activation in response to demyelination in vivo.

Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro.

Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a presumed autoimmune disease directed against central nervous system (CNS) myelin, in which diet and obesity are implicated as risk factors. Immune responses can be influenced by molecules produced by fat cells, called adipokines. Adiponectin is an adipokine with anti-inflammatory effects.

CXCL13 is a biomarker of inflammation in multiple sclerosis, neuromyelitis optica, and other neurological conditions.

CXCL13, a B-cell chemokine, has been proposed as a biomarker in a variety of conditions, some of which can mimic multiple sclerosis and can have very high levels. In this case-control study, cerebrospinal fluid (CSF) CXCL13 was elevated in multiple sclerosis, neuromyelitis optica and other inflammatory neurological controls compared with noninflammatory controls. Levels did not differentiate disease groups.

Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity.

Experimental autoimmune encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), is dependent upon the activation and effector functions of autoreactive CD4 T cells. Multiple interactions between CD4 T cells and major histocompatibility class II (MHCII)+ antigen presenting cells (APCs) must occur in both the periphery and central nervous system (CNS) to elicit autoimmunity. The identity of the MHCII+ APCs involved throughout this process remains in question.

Elevated intrathecal myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis.

Objective: To evaluate antibodies to myelin oligodendrocyte glycoprotein (MOG) in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and control individuals.

Design: Prospective case-control series.

Setting: Academic referral center.

B cells limit epitope spreading and reduce severity of EAE induced with PLP peptide in BALB/c mice.

The role of B cells and antibody in experimental autoimmune encephalomyelitis (EAE) appears to differ based on the identity and state (protein vs. encephalitogenic peptide) of the inducing antigen and the strain of mouse utilized. The involvement of B cells in the induction of EAE by peptides of proteolipid protein (PLP) in BALB/c mice was investigated.