Tailoring Rituximab According to CD27-Positive B-Cell versus CD19-Positive B-Cell Monitoring in Neuromyelitis Optica Spectrum Disorder and MOG-Associated Disease: Results from a Single-Center Study.

Introduction: B-cell-depleting agents have been widely used for neuromyelitis optica spectrum disorder (NMOSD) and MOG-associated diseases (MOGAD), but no consensus exists on the optimal dose and frequency of treatment administration. The aim of our study was to evaluate the effect of a Rituximab (RTX) personalized treatment approach based on CD27-positive B-cell monitoring on efficacy, safety, and infusion rates.

Methods: This is a retrospective, uncontrolled, single-center study including patients with NMOSD and MOGAD treated with RTX at a tertiary multiple sclerosis center at the San Luigi University Hospital, Orbassano, Italy.

The impact of pre-freezing storage time and temperature on gene expression of blood collected in EDTA tubes.

Background: Blood is a common source of RNA for gene expression studies. However, it is known to be vulnerable to pre-analytical variables. Although RNA stabilization systems have been shown to reduce such influence, traditional EDTA tubes are still widely used since they are less expensive and enable to study specific leukocyte populations.

Serum neurofilament light chain levels in healthy individuals: A proposal of cut-off values for use in multiple sclerosis clinical practice.

Background: Serum Neurofilament Light (sNFL) is the most promising marker for patient's monitoring in Multiple Sclerosis (MS). However, operating reference values for use in clinical practice are still lacking. Here, we defined sNFL reference cut-off values in a cohort of healthy controls (HC) and assessed their performance in Multiple Sclerosis (MS) patients, as well as the intra-individual sNFL variability.

Autologous Hematopoietic Stem Cell Transplantation (AHSCT): Standard of Care for Relapsing-Remitting Multiple Sclerosis Patients.

Autologous hematopoietic stem cell transplantation (AHSCT) has been used in the treatment of highly active multiple sclerosis (MS) for over two decades. It has been demonstrated to be highly efficacious in relapsing-remitting (RR) MS patients failing to respond to disease-modifying drugs (DMDs). AHSCT guarantees higher rates of no evidence of disease activity (NEDA) than those achieved with any other DMDs, but it is also associated with greater short-term risks which have limited its use.

Immunomodulatory Effect of Pregnancy on Leukocyte Populations in Patients With Multiple Sclerosis: A Comparison of Peripheral Blood and Decidual Placental Tissue.

Pregnancy is a naturally occurring disease modifier of multiple sclerosis (MS) associated with a substantial reduction in relapse rate. To date, attempts to explain this phenomenon have focused on systemic maternal immune cell composition, with contradictory results. To address this matter, we compared the immunomodulatory effects of pregnancy on five leukocyte populations (i.

Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10years in responder multiple sclerosis patients.

Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14CD163 monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months.

Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis.

The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi-quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs).

Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica.

Objective: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD).

Development of a Short Version of MSQOL-54 Using Factor Analysis and Item Response Theory.

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54, 52 items grouped in 12 subscales plus two single items) is the most used MS specific health related quality of life inventory.

Objective: To develop a shortened version of the MSQOL-54.

Methods: MSQOL-54 dimensionality and metric properties were investigated by confirmatory factor analysis (CFA) and Rasch modelling (Partial Credit Model, PCM) on MSQOL-54s completed by 473 MS patients.

PML risk stratification using anti-JCV antibody index and L-selectin.

Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters.

Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.

Background: The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ.

CD19 mRNA quantification improves rituximab treatment-to-target approach: a proof of concept study.

We compared pre-amplification (PA) RT-PCR blood CD19 mRNA quantification with flow cytometry (FC), to personalize rituximab re-treatment in neuromyelitis optica spectrum disorders (NMOSDs) patients. 47 blood samples from 3 NMOSDs patients were studied. PA-RT-PCR quantified CD19 in all samples, and a positivity threshold was defined, whereas CD19+ B cells were under threshold in 31/47 samples by FC.

Multiple Sclerosis State of the Art (SMART): A Qualitative and Quantitative Analysis of Therapy's Adherence, Hospital Reliability's Perception, and Services Provided Quality.

The purpose of this study was to assess the adherence to therapy in patients with relapsing remitting multiple sclerosis (RR-MS) and to analyze the possible influence of factors such as hospital care and patients socioeconomic status. Two hundred eighty-five patients with RR-MS according to Mc Donald's criteria and naïve disease-modifying drugs (DMDs) naïve were enrolled. Two self-administered questionnaires addressing the management of patients at therapy prescription and the personal perception of the daily life changes caused by DMDs were administered at months 3 and 12.

Evaluation of a multiparametric immunofluorescence assay for standardization of neuromyelitis optica serology.

Background: Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the central nervous system, which predominantly affects the optic nerves and spinal cord. In a majority of cases, NMO is associated with antibodies to aquaporin-4 (AQP4) (termed NMO-IgG).

Aims: In this study, we evaluated a new multiparametric indirect immunofluorescence (IIF) assay for NMO serology.

Loss of braking signals during inflammation: a factor affecting the development and disease course of multiple sclerosis.

Background: In a recent genome-wide transcriptional analysis, we identified a gene signature for multiple sclerosis (MS), which reverted back to normal during pregnancy. Reversion was particularly evident for 7 genes: SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1, most of which encode negative regulators of inflammation.

Objectives: To corroborate dysregulation of genes, to evaluate the prognostic value of genes, and to study modulation of genes during different treatments.

Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy.

The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha-synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of iNOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons.

High dose levodopa therapy is not toxic in multiple system atrophy: experimental evidence.

Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors.