Publications by authors named "Catherine Larochelle"
Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying -regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to -regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls.
View Article and Find Full Text PDFAutoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here we report the discovery of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens.
View Article and Find Full Text PDFArticle Synopsis
- * This study proposes that sustainable adoption of improved bean varieties can occur through a coordinated effort involving private sector-led multi-stakeholder platforms that connect seed production to grain markets.
- * Research indicates that membership in these platforms, along with factors like contractual agreements and extension services, significantly boosts the supply of certified common bean seeds, highlighting the need for supportive policies.
Article Synopsis
- The COVID-19 pandemic has severely impacted immunosuppressed individuals, such as solid organ transplant recipients and those undergoing cancer treatment, leading to worse health outcomes and higher mortality rates.
- Due to challenges in studying these vulnerable populations, researchers created a mathematical model to simulate immune responses and analyzed virtual patient cohorts that mirrored clinical data from cancer and immunosuppressed patients.
- The model revealed that severe cases in these groups exhibited reduced CD8+ T cells, delayed type I interferon peaks, and higher tissue damage, suggesting that immune dysfunction is a critical factor in COVID-19 severity for cancer patients.
Efficacy of cannabinoids compared to the current standard treatments on symptom relief in persons with multiple sclerosis (CANSEP trial): study protocol for a randomized clinical trial.
Amel Zertal Kanza Alami Marrouni Nathalie Arbour Didier Jutras-Aswad Marie-Pascale Pomey Catherine Larochelle
Front Neurol
July 2024
Article Synopsis
- Multiple sclerosis (MS) is a debilitating disease affecting over 90,000 Canadians, and current treatments only offer limited relief; many patients turn to cannabis for symptom management despite the lack of solid scientific backing.
- This clinical trial seeks to evaluate the effectiveness of various doses of cannabinoids (THC and CBD), both individually and in combination, for alleviating spasticity in MS patients, comparing results against a placebo group.
- The study will involve 250 participants and utilize a double-blind, randomized design, measuring outcomes such as self-reported spasticity, pain, and quality of life over a period of four weeks, with potential for an additional 12-week treatment phase for those who respond well.
Article Synopsis
- A 40-year-old man with autoimmune encephalitis and a thymoma experienced severe neurological symptoms and multiple relapses despite initial treatments, which included thymectomy and first-line immunotherapy.
- Initial antibody tests revealed acetylcholine receptor and titin antibodies, but further testing eventually identified anti-GABA receptor antibodies.
- The case highlights the challenge of diagnosing and treating autoimmune encephalitis with coexisting antibodies, underscoring the need for targeted second-line therapies like rituximab in severe cases.
Article Synopsis
- The study aims to create and validate a clinical risk score to predict renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC).
- Data from 2420 participants was analyzed using logistic regression, taking into account early-onset clinical signs, sex, and genetic mutations to develop risk scores for AML and LAM.
- Results showed that risk scores effectively predicted the likelihood of AML and LAM, with excellent calibration and strong discrimination, suggesting potential for personalized preventative care and screening in TSC patients.
Article Synopsis
- - The study analyzes plasma samples from 318 COVID-19 patients to understand how RNAemia, delayed antibody responses, and inflammation affect patient outcomes, revealing four distinct patient clusters based on severity and survival probability.
- - Critically ill patients were categorized into good prognosis and high-fatality clusters, while non-critical survivors were divided into high and low early antibody responders, each showing different patterns in antibody development and inflammation.
- - The findings indicate that high-fatality patients have specific genomic signatures linked to severe COVID-19, and both critical and non-critical patients with delayed antibody responses exhibit persistent interferon (IFN) activity, suggesting that high IFN levels might hinder the body's ability to build effective immunity.
Article Synopsis
- * Researchers used single-cell transcriptomics to compare the gene expression of reactive ependymal cells with that of reactive astrocytes in a model of autoimmune-mediated neuroinflammation, revealing key genes linked to glial reactivity.
- * The study suggested that the reactivity of ependymal cells might share similarities with that of astrocytes across various disease contexts, highlighting a potential conserved response, with plans for future investigations into the mechanisms of this reactivity and its impacts.
Article Synopsis
- Dimensionality reduction methods like PHATE, t-SNE, and UMAP help visualize complex biological data, but they often do so without the guidance of expert labels.
- The new method RF-PHATE combines expert knowledge with unsupervised techniques by using random forests to create low-dimensional visualizations that emphasize important data relationships while filtering out irrelevant features.
- RF-PHATE is effective for large datasets and has been successfully applied in multiple case studies, showing its ability to handle time-series data in multiple sclerosis research, analyze noisy Raman spectral data, and connect geometric structures with COVID-19 outcomes.
Article Synopsis
- The Biobanque québécoise de la COVID-19 (BQC19) is a provincial initiative aimed at collecting and sharing biological samples and clinical data related to COVID-19, but faced challenges with high participant dropout rates.
- A qualitative study involving interviews with 23 BQC19 participants and 17 professionals explored motivations for participation and reasons for attrition, revealing evolving motivations like contributing to science and barriers such as logistical issues, negative attitudes, and fears of clinical settings.
- The findings indicate that the pandemic environment significantly influenced both participant engagement and the research teams' ability to maintain participation, highlighting the importance of understanding these dynamics in crisis settings.
Article Synopsis
- The blood-brain barrier (BBB), created by brain endothelial cells, controls what can enter the central nervous system (CNS) and is crucial for maintaining blood flow in response to neuronal activity.
- In multiple sclerosis (MS), the BBB is first damaged by inflammation and allows harmful immune cells into the CNS, leading to various symptoms, and later, problems with blood flow can result in grey matter loss.
- Genetic and environmental factors may cause dysfunction in brain endothelial cells, contributing to BBB damage, but potential therapies, such as monoclonal antibodies and mesenchymal stromal cells, may help to prevent or repair this damage in MS patients.
Article Synopsis
- Multiple sclerosis (MS) is an autoimmune disease that damages myelin in the central nervous system, leading to injury of brain and spinal cord cells due to immune cell infiltration, particularly by pro-inflammatory Th17 cells.
- The study investigated how these Th17 cells interact with oligodendrocytes (the myelin-producing cells) through specific adhesion molecules, finding that the presence of certain molecules like ALCAM helps these cells adhere, which can lead to cell death.
- Results showed that in the presence of inflammatory cytokines or activated T cells, the expression of MCAM decreased, offering protective insights that targeting ALCAM could reduce harmful interactions between Th17 cells and oligodendrocytes, potentially leading to new therapeutic strategies for
Article Synopsis
- The global MS population is aging, with peak prevalence observed in individuals aged 55-65, leading to shifts in disease characteristics and progression.
- Aging impacts the pathophysiology of MS, causing a consistent worsening of disability around age 50, which is independent of prior disease duration.
- Older MS patients face unique challenges, such as diminished treatment efficacy, increased adverse effects from medications, and a higher burden of comorbidities, necessitating individualized treatment approaches.
Article Synopsis
- MOGAD is a newly identified neuroinflammatory disease characterized by the presence of anti-MOG antibodies, with symptoms varying widely among patients.
- A study conducted in Quebec found a prevalence of 0.52 cases per 100,000 people, with optic neuritis and acute disseminated encephalomyelitis being the most common initial symptoms.
- Only 38% of patients fully recovered within 4 weeks, and a significant number of patients experienced relapses and residual deficits, indicating a serious disease course for many.*
Article Synopsis
- The study examines the role of inflammation in drug-resistant epilepsy (DRE) and evaluates how two new anti-epileptic drugs (AEDs), brivaracetam and lacosamide, affect immune cell activation.
- Research shows that both AEDs do not negatively impact the survival or activation of immune cells at lower doses, but higher doses reduce CD8 T cell proliferation and certain markers.
- Although these AEDs do not delay the onset of experimental autoimmune encephalomyelitis (EAE), they improve the disease's clinical course, suggesting they may help reduce neuroaxonal damage in DRE.
Article Synopsis
- - The study investigates changes in T lymphocytes related to multiple sclerosis (MS) and focuses on the NKG2D pathway, which is crucial for CD4 and CD8 T cell activation, revealing that its activity varies across different forms of MS (RRMS, SPMS, and PPMS).
- - Using flow cytometry and microscopy, researchers found that NKG2D T lymphocytes are less abundant in RRMS patients compared to healthy controls, and their proportion decreases with age in PPMS patients due to reduced γδ and αβ CD4CD8 populations.
- - Blocking NKG2D in co-cultured CD8 T lymphocytes and astrocytes resulted in increased mobility and a shift from long-lasting
Article Synopsis
- * A survey of alumni from the University of Montreal's CIP showed high satisfaction rates (85% overall, 84% for research skills), with 63% becoming independent investigators who secured funding.
- * Despite positive outcomes, the study identified areas for improvement, particularly in supporting career transitions from the CIP to independent roles, which is critical for developing successful clinician-investigators.
Article Synopsis
- Multiple sclerosis (MS) is a complex disease involving immune cell infiltration into the central nervous system (CNS), but the exact mechanisms of this process are not well understood.
- This study used single-cell RNA sequencing and analyses of endothelial cells in an animal model of MS to uncover gene expression patterns related to neuroinflammation, particularly focusing on venous endothelial cells (ECs).
- Findings indicated that venous ECs play a significant role in neuroinflammation, with notable gene expression changes and molecular interactions identified, contributing to a better understanding of the processes that allow immune cells to enter the brain in MS.*
Article Synopsis
- The study investigates how autoreactive white blood cells, specifically CD4+ T lymphocytes, cross the blood-brain barrier, contributing to multiple sclerosis (MS) pathology.
- Researchers identified a protein called MCAM on brain endothelial cells that helps facilitate this migration of immune cells during neuroinflammation.
- Targeting MCAM could offer a new therapeutic strategy for treating MS by preventing the recruitment of these harmful T lymphocytes from the blood.
Article Synopsis
- GM-CSF plays a significant role in chronic inflammatory diseases like multiple sclerosis (MS) by affecting myeloid cell functions, specifically monocyte-derived macrophages (MDMs) and microglia.
- The study found that GM-CSF increases IL-15 expression in MDMs from both healthy individuals and MS patients, as well as in human microglia, which may enhance the immune response against MS.
- Notably, while GM-CSF-stimulated MDMs elevate CD8 T lymphocytes' production of effector molecules, this enhancement occurs independently of IL-15, suggesting that GM-CSF influences myeloid cells through multiple pathways.
CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.
Antoine Philippe Fournier Stephanie Zandee Marc Charabati Evelyn Peelen Olivier Tastet Catherine Larochelle
Neurol Neuroimmunol Neuroinflamm
November 2022
Article Synopsis
- - The study investigates the role of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the central nervous system (CNS) of patients with multiple sclerosis (MS), focusing on how it contributes to CNS damage.
- - Researchers found that CLMP expression was significantly heightened in both the endothelial cells and immune cells of MS patients, particularly in active brain lesions, indicating its involvement in the inflammatory response associated with MS.
- - Blocking CLMP with specific antibodies reduced immune cell migration across brain endothelial cells in laboratory tests, suggesting that targeting CLMP may offer a potential therapeutic approach for managing MS-related inflammation.
Article Synopsis
- Interleukin-27 (IL-27) can cause both pro-inflammatory and anti-inflammatory effects and is found at higher levels in the central nervous system of multiple sclerosis (MS) patients, but its specific role in neuroinflammation is not fully understood.
- * The study investigates how astrocytes respond to IL-27 and how this affects their interaction with activated T lymphocytes under both inflamed and non-inflamed conditions.
- * Results show that IL-27 exposure leads to increased immune-related gene expression in astrocytes, enhances the secretion of certain chemokines, and alters the activation status and motility of CD8 T lymphocytes, suggesting more dynamic interactions between these cells in the context of inflammation.
Article Synopsis
- Single-cell RNA sequencing revealed that mature oligodendrocytes (MOLs) in the human brain and spinal cord have distinct subpopulations based on region and age.
- Spinal cord MOLs showed increased immune-related markers, while subventricular zone MOLs had more development-linked transcription factors, indicating unique characteristics across different brain regions.
- Pediatric MOLs, particularly those from children under 5, exhibited higher expression of genes related to development and immune activity, suggesting that younger MOLs are influenced by both developmental and environmental factors.
Article Synopsis
- The CRISPR-Cas9 system has transformed the creation of genetically engineered animal models, particularly conditional alleles, which are complex due to the need for precise genome modifications using two guides.
- Researchers developed a modified sequential electroporation method that successfully produced conditional allele mouse models for eight different genes using two approaches: consecutive and non-consecutive electroporation.
- The results showed varying targeting efficiencies, with both strategies yielding successful models that could enhance the generation of conditional allele models in future research.