A5035144941- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Renal Transplantation Outcomes and Treatments
- Renal Diseases and Glomerulopathies
- Systemic Sclerosis and Related Diseases
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- IL-33, ST2, and ILC Pathways
- Immunodeficiency and Autoimmune Disorders
- Atherosclerosis and Cardiovascular Diseases
- Autoimmune Bullous Skin Diseases
- Immunotherapy and Immune Responses
- Complement system in diseases
- interferon and immune responses
- Hormonal Regulation and Hypertension
- Birth, Development, and Health
- Xenotransplantation and immune response
- Dialysis and Renal Disease Management
- Phagocytosis and Immune Regulation
- Organ Transplantation Techniques and Outcomes
University Health Network
2015-2024
Toronto General Hospital
2023-2024
Krembil Research Institute
2016-2024
Toronto General Hospital Research Institute
2024
Zero to Three
2023
University of Toronto
2015-2018
Arthritis Research Centre of Canada
2017
Toronto Western Hospital
2015
Diabetic kidney disease (DKD) is the main cause of chronic (CKD) and progresses faster in males than females. We identify sex-based differences metabolism blood metabolome male female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy displayed increased mitochondrial respiration, oxidative stress, apoptosis, greater injury when exposed to high glucose compared PTECs Male showed glutamine fluxes TCA cycle, whereas pyruvate content. The PTEC...
Elevated levels of serum interferon-α (IFNα) and the disruption B cell tolerance are central to systemic lupus erythematosus (SLE) immunopathogenesis; however, relationship between these 2 processes remains unclear. The purpose this study was investigate impact elevated IFNα on mechanisms in vivo determine whether any changes observed were due direct effect cells.Two classical mouse models used conjunction with an adenoviral vector encoding mimic sustained elevations seen SLE. role...
Diagnosis of systemic autoimmune rheumatic diseases (SARD) relies on the presence hallmark anti-nuclear antibodies (ANA), many which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals, most whom will not develop SARD. Here, we examined a unique cohort asymptomatic ANA+ individuals to determine whether they share any cellular immunologic features Healthy ANA− controls and (ANA ≥1:160 by immunofluorescence) participants with no SARD...
The development and progression of systemic lupus erythematosus is mediated by the complex interaction genetic environmental factors. To decipher genetics that contribute to pathogenesis production pathogenic autoantibodies, our lab has focused on generation congenic lupus-prone mice derived from New Zealand Black (NZB) strain. Previous work shown an NZB-derived chromosome 4 interval spanning 32 151 Mb led expansion CD5+ B Natural Killer T (NKT) cells, could suppress autoimmunity when...
Systemic Autoimmune Rheumatic Diseases (SARDs) are characterized by the production of anti-nuclear antibodies (ANAs). ANAs also seen in healthy individuals and can be detected years before disease onset SARD. Both immunological changes that promote development clinical symptoms SARD those prevent autoimmunity asymptomatic ANA + (ANA NS) remain largely unexplored. To address this question, we used flow cytometry to examine peripheral blood immune populations individuals, with without SARD,...
Objective The aim of this study was to determine the immunologic profile associated with disease flares in patients systemic lupus erythematosus (SLE) and investigate clinical significance any differences observed between during following a flare. Methods Multiparameter flow cytometry used examine 47 immune populations within peripheral blood 16 healthy controls, 25 clinically quiescent SLE, 46 SLE experiencing flare at baseline 6‐ 12‐month follow‐up visits. Unsupervised clustering identify...
Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and rapidly activated produce large quantities of cytokines chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes provide key homotypic signaling lymphocyte activation (SLAM) family members. However, role SLAM receptors in differentiation effector subsets has not been explored. In this article, we show C57BL/6 mice...
We showed previously that C57BL/6 congenic mice with an introgressed homozygous 70 cM (125.6 Mb) to 100 (179.8 interval on c1 from the lupus-prone New Zealand Black (NZB) mouse develop high titers of antinuclear Abs and severe glomerulonephritis. Using subcongenic mice, we found a genetic locus in 88-96 region was associated altered dendritic cell (DC) function synergized T functional defects promote expansion pathogenic proinflammatory subsets. In this article, show promoter NZB gene...
<h3>Background</h3> Elevated levels of interferons (IFN) are a hallmark Systemic Lupus Erythematosus (SLE) and have been linked to disease flares, but the precise mechanisms by which this occurs remain unclear. To address question, we examined association between IFN-induced proteins (IIPs) immune changes in flaring quiescent SLE patients at single cell level. <h3>Methods</h3> A 41-marker panel was developed that enabled measurement IIPs peripheral blood mononuclear (PBMC) populations using...
Introduction Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient biospecimens, integration of these datasets challenging, which represents considerable barrier to advancing our understanding mechanisms loss. Methods To facilitate integration, we created curated database containing all open-access from human transplant studies, termed NephroDIP...
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody Transgenes soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto background various examined. We found that c1(96-100) produced increased levels IgM IgG antibodies compared had higher...
Manion, Kieran; Allen, Maya A.; Freixas, Sergi Clotet; John, Rohan; Konvalinka, Ana Author Information
<h3>Background</h3> The diagnosis of Systemic Autoimmune Rheumatic Diseases (SARD), including Lupus Erythematosus (SLE), relies on the presence ANAs, many which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals most whom will not develop SARD. A number cellular immune changes SARD, and thus could constitute potential biomarkers/treatment targets for however it is known at what point disease progression these develop. <h3>Methods</h3>...
Background Systemic lupus erythematosus (SLE) is a severe autoimmune disease in which immune tolerance defects drive production of pathogenic anti-nuclear autoantibodies. Anergic B cells are considered potential source these autoantibodies due to their autoreactivity and overrepresentation SLE patients. Studies lupus-prone mice have shown that genetic mediating autoimmunity can breach cell anergy, but how this occurs with regards endogenous nuclear antigen remains unclear. We investigated...
<h3>Background</h3> Previous studies suggest substantial immunologic heterogeneity in lupus. However, the majority of these were cross-sectional nature. Here we followed flaring and quiescent patients longitudinally to determine how their profile changes over time. <h3>Methods</h3> Forty-seven SLE with a recent flare (change clinical SLEDAI ≥ 2 past month that prompted change therapy), 25 (clinical = 0 for 1 year no increase immunosuppressive treatment , ≤ 10 mg prednisone, matched disease...
<h3>Background</h3> ANA<sup>+</sup>systemic autoimmune rheumatic diseases (SARD), including SLE, have a prolonged pre-clinical phase during which ANAs can be detected in the absence of clinical symptoms. are also seen healthy individuals, most whom will not progress to SARD. The immunological changes that promote development symptoms SARD and conversely maintain benign autoimmunity asymptomatic ANA<sup>+</sup> individuals (ANA<sup>+</sup>NS) remain largely unexplored. To address this...