Single center, real-world retrospective study of CAR-T cell therapy for relapsed/refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven.

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line.

Single center, real-world retrospective study of CAR-T cell therapy for relapsed/refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven.

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line.

CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis.

Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five myeloid markers - CHIT1, CHI3L1, sTREM2, GPNMB and CCL18 - in the cerebrospinal fluid (CSF) at diagnostic lumbar puncture in a longitudinal cohort of 192 MS patients. Through mixed-effects and machine learning models, we show that CHIT1 is a robust predictor for faster disability progression.

Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired.

A targeted sequencing extension for transcript genotyping in single-cell transcriptomics.

As no existing methods within the single-cell RNA sequencing repertoire combine genotyping of specific genomic loci with high throughput, we evaluated a straightforward, targeted sequencing approach as an extension to high-throughput droplet-based single-cell RNA sequencing. Overlaying standard gene expression data with transcript level genotype information provides a strategy to study the impact of genetic variants. Here, we describe this targeted sequencing extension, explain how to process the data and evaluate how technical parameters such as amount of input cDNA, number of amplification rounds, and sequencing depth influence the number of transcripts detected.

Frequent somatic mosaicism in T lymphocyte subsets in individuals with and without multiple sclerosis.

Background: Somatic variants are variations in an individual's genome acquired after the zygotic stadium and result from mitotic errors or not (fully) repaired DNA damage.

Objectives: To investigate whether somatic mosaicism in T lymphocyte subsets is enriched early in multiple sclerosis (MS).

Methods: We identified somatic variants with variant allele fractions ≥1% across the whole exome in CD4 and CD8 T lymphocytes of 21 treatment-naive MS patients with <5 years of disease duration and 16 partially age-matched healthy controls.

Optical coherence tomography as a prognostic tool for disability progression in MS: a systematic review.

Since multiple sclerosis (MS) is characterized by an unpredictable disease course, accurate prognosis and personalized treatment constitute an important challenge in clinical practice. We performed a qualitative systematic review to assess the predictive value of retinal layer measurement by spectral-domain optical coherence tomography (SD-OCT) in MS patients. Longitudinal MS cohort studies that determined the risk of clinical deterioration based on peripapillary retinal nerve fiber layer (pRNFL) and/or macular ganglion cell-inner plexiform layer (mGCIPL) atrophy were included.

Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016-2020).

Background: Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors.

Antiviral treatment with fluoxetine for rituximab-associated chronic echovirus 13 meningoencephalitis and myofasciitis.

Background And Purpose: Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated.

Methods: Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry.

Neurocysticercosis: An Uncommon Cause of Acute Supratentorial Hydrocephalus.

We report a 29-year-old woman with acute supratentorial hydrocephalus due to intraventricular neurocysticercosis (NC). Aqueductal stenosis due to web formation and a free floating intraventricular cyst with scolex were pathognomonic and led to the diagnosis of NC. Worldwide, NC is the most important parasitic infection of the central nervous system but is very uncommon in non-endemic regions.

Effects of Vitamin D and Body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis: A Mendelian Randomization Study.

Background And Objectives: Decreased vitamin D levels and obesity are associated with an increased risk for multiple sclerosis (MS). However, whether they also affect the disease course after onset remains unclear. With larger data sets now available, we used Mendelian randomization (MR) to determine whether serum 25-hydroxyvitamin D (25OHD) and body mass index (BMI) are causally associated with MS risk and, moving beyond susceptibility toward heterogeneity, with relapse hazard.

Body Mass Index, Interleukin-6 Signaling and Multiple Sclerosis: A Mendelian Randomization Study.

Objectives: We explored whether genetically predicted increased body mass index (BMI) modulates multiple sclerosis (MS) risk through interleukin-6 (IL-6) signaling.

Methods: We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets for BMI, IL-6 signaling, IL-6 levels and c-reactive protein (CRP) levels as exposures and estimated their effects on risk of MS from GWAS data from the International Multiple Sclerosis Genetics Consortium (IMSGC) in 14,802 MS cases and 26,703 controls.

Results: In univariable MR analyses, genetically predicted increased BMI and IL-6 signaling were associated with higher risk of MS (BMI: odds ratio (OR) = 1.

Environmental risk factors in multiple sclerosis: bridging Mendelian randomization and observational studies.

Multiple sclerosis (MS) is a complex disease with both genetic variants and environmental factors involved in disease susceptibility. The main environmental risk factors associated with MS in observational studies include obesity, vitamin D deficiency, Epstein-Barr virus infection and smoking. As modifying these environmental and lifestyle factors may enable prevention, it is important to pinpoint causal links between these factors and MS.

Treatment-Induced BAFF Expression and B Cell Biology in Multiple Sclerosis.

Although fingolimod and interferon-β are two mechanistically different multiple sclerosis (MS) treatments, they both induce B cell activating factor (BAFF) and shift the B cell pool towards a regulatory phenotype. However, whether there is a shared mechanism between both treatments in how they influence the B cell compartment remains elusive. In this study, we collected a cross-sectional study population of 112 MS patients (41 untreated, 42 interferon-β, 29 fingolimod) and determined B cell subsets, cell-surface and RNA expression of BAFF-receptor (BAFF-R) and transmembrane activator and cyclophilin ligand interactor (TACI) as well as plasma and/or RNA levels of BAFF, BAFF splice forms and interleukin-10 (IL-10) and -35 (IL-35).

Genetic Variation in WNT9B Increases Relapse Hazard in Multiple Sclerosis.

Objective: Many multiple sclerosis (MS) genetic susceptibility variants have been identified, but understanding disease heterogeneity remains a key challenge. Relapses are a core feature of MS and a common primary outcome of clinical trials, with prevention of relapses benefiting patients immediately and potentially limiting long-term disability accrual. We aim to identify genetic variation associated with relapse hazard in MS by analyzing the largest study population to date.

Quantitative MRI phenotypes capture biological heterogeneity in multiple sclerosis patients.

Magnetization transfer ratio (MTR) and brain volumetric imaging are (semi-)quantitative MRI markers capturing demyelination, axonal degeneration and/or inflammation. However, factors shaping variation in these traits are largely unknown. In this study, we collected a longitudinal cohort of 33 multiple sclerosis (MS) patients and extended it cross-sectionally to 213.

CHIT1 at Diagnosis Reflects Long-Term Multiple Sclerosis Disease Activity.

Objective: Evidence for a role of microglia in the pathogenesis of multiple sclerosis (MS) is growing. We investigated association of microglial markers at time of diagnostic lumbar puncture (LP) with different aspects of disease activity (relapses, disability, magnetic resonance imaging parameters) up to 6 years later in a cohort of 143 patients.

Methods: In cerebrospinal fluid (CSF), we measured 3 macrophage and microglia-related proteins, chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1 or YKL-40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), as well as a marker of neuronal damage, neurofilament light chain (NfL), using enzyme-linked immunosorbent assay and electrochemiluminescence.

A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease.

The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives, and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization.

Genetic Architecture of Adaptive Immune System Identifies Key Immune Regulators.

The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%-20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation.

LncRNAs expression profile in peripheral blood mononuclear cells from multiple sclerosis patients.

LncRNA PCR arrays containing 90 common LncRNAs were used to screen lncRNA expression levels in PBMC from a discovery population of patients with MS. Data from discovery and replications cohorts showed a generalized dysregulation of lncRNA levels in MS patients compared with controls. MALAT1, MEG9, NRON, ANRIL, TUG1, XIST, SOX2OT, GOMAFU, HULC, BACE-1AS were significantly downregulated in MS patients in comparison with controls.

A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis.

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies.

Correction to: Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus.

The article Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus, written by Lambert et al., was originally published electronically on the publisher's internet portal on 27 January 2018 without open access.