A5080205405- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- IL-33, ST2, and ILC Pathways
- Spondyloarthritis Studies and Treatments
- Diabetes Management and Research
- Pediatric health and respiratory diseases
- Parasites and Host Interactions
- Rheumatoid Arthritis Research and Therapies
- Diabetes and associated disorders
- Psoriasis: Treatment and Pathogenesis
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Pancreatic function and diabetes
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Eosinophilic Esophagitis
- Immune responses and vaccinations
- Chemokine receptors and signaling
- Complement system in diseases
- Inflammasome and immune disorders
- NF-κB Signaling Pathways
The University of Queensland
2014-2023
Princess Alexandra Hospital
2012-2022
Translational Research Institute
2013-2022
Stellenbosch University
2003-2014
South African Reserve Bank
2014
St. James's Hospital
2009-2013
Trinity College Dublin
2009-2013
German Centre for Cardiovascular Research
2010
Charité - Universitätsmedizin Berlin
2010
Tokyo Women's Medical University
2010
Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)-DRB1 locus that possesses shared susceptibility epitope (SE) and citrullination of self-antigens. We show how citrullinated aggrecan vimentin epitopes bind to HLA-DRB1*04:01/04. Citrulline was accommodated within electropositive P4 pocket HLA-DRB1*04:01/04, whereas electronegative RA-resistant HLA-DRB1*04:02 allomorph interacted arginine or citrulline-containing epitopes. Peptide elution studies revealed...
In animals, immunomodulatory dendritic cells (DCs) exposed to autoantigen can suppress experimental arthritis in an antigen-specific manner. rheumatoid (RA), disease-specific anti-citrullinated peptide autoantibodies (ACPA or anti-CCP) are found the serum of about 70% RA patients and strongly associated with HLA-DRB1 risk alleles. This study aimed explore safety biological clinical effects autologous DCs modified a nuclear factor κB (NF-κB) inhibitor four citrullinated antigens, designated...
Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role surface layer proteins (SLPs) this disease has not yet been fully explored. aim study was to investigate a for SLPs recognition C. subsequent activation immune system. Bone marrow derived dendritic cells (DCs) exposed were assessed production inflammatory cytokines, expression cell markers their ability generate T helper (Th) responses. DCs isolated from...
Abstract Introduction Anti-citrullinated peptide antibodies are found in rheumatoid arthritis (RA) patients with HLA-DRβ chains encoding the shared epitope (SE) sequence. Citrullination increases self-antigen immunogenicity, through increased binding affinity to SE-containing HLA-DR molecules. To characterise T-cell autoreactivity towards citrullinated self-epitopes, we profiled responses of SE + healthy controls and RA unmodified epitopes four autoantigens. Methods We compared proliferative...
The incidence of allergy and asthma in developed countries is on the increase this trend looks likely to continue. CD4+ T helper 2 (Th2) cells are major drivers these diseases their commitment controlled by cytokines such as interleukin 4, which turn regulated suppressor cytokine signaling (SOCS) proteins. We report that SOCS2−/− show markedly enhanced Th2 differentiation. mice, well RAG-1−/− mice transferred with cells, exhibit elevated type responses after helminth antigen challenge....
Autoimmune diseases resulting from MHC class II–restricted autoantigen-specific T cell immunity include the systemic inflammatory autoimmune conditions rheumatoid arthritis and vasculitis. While currently treated with broad-acting immunosuppressive drugs, a preferable strategy is to regulate antigen-specific effector cells (Teffs) restore tolerance by exploiting DC antigen presentation. We targeted draining lymph node (dLN) phagocytic DCs using liposomes encapsulating 1α,25-dihydroxyvitamin...
Objective Ankylosing spondylitis ( AS ) is a common spondyloarthropathy primarily affecting the axial skeleton and strongly associated with HLA –B*27 carriage. Genetic evidence implicates both autoinflammatory processes autoimmunity against an –restricted autoantigen in immunopathology. In addition to articular symptoms, up 70% of patients present concurrent bowel inflammation, suggesting that adverse interactions between genetically primed host immune system gut microbiome contribute...
BACKGROUNDAntigen-specific regulation of autoimmune disease is a major goal. In seropositive rheumatoid arthritis (RA), T cell help to autoreactive B cells matures the citrullinated (Cit) antigen-specific immune response, generating RA-specific V domain glycosylated anti-Cit protein antibodies (ACPA VDG) before onset. Low or escalating antigen administration under "sub-immunogenic" conditions favors tolerance. We explored safety, pharmacokinetics, and immunological clinical effects s.c....
Background. IL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade IL-6R with monoclonal antibody tocilizumab would slow loss residual β function in newly diagnosed patients.
Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the a prospective cohort RA, first-degree relatives (FDR) healthy controls (HC), then genomically functionally characterised streptococcal species from each group understand their potential contribution RA development.After DNA extraction tongue swabs, targeted 16S rRNA gene sequencing...
Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV the host immune system is one main determinants infection outcome. Chemokines play relevant roles in antiviral response immunopathology, but modulation chemokine function by not well understood. We have addressed mediated HSV. By using surface plasmon resonance crosslinking assays we show secreted glycoprotein...
ABSTRACT Trichinella spiralis is a highly destructive parasitic nematode that invades and destroys intestinal epithelial cells, injures many different tissues during its migratory phase, occupies transforms myotubes the final phase of life cycle. We set out to investigate role in immunity innate receptors for potential pathogen- or danger-associated molecular patterns (PAMPs DAMPs). Focusing on MyD88-dependent receptors, which include Toll-like (TLRs) interleukin-1 (IL-1) family members, we...
β-Interferons (IFN-βs) represent one of the first line treatments for relapsing-remitting multiple sclerosis, slowing disease progression while reducing frequency relapses. Despite this, more effective, well tolerated therapeutic strategies are needed. Cannabinoids palliate experimental autoimmune encephalomyelitis (EAE) symptoms and have potential in MS patients although precise molecular mechanism these effects is not understood. Toll-like receptor (TLR) signaling controls innate immune...
The objective of this study was to determine whether there is a relationship between emotional intelligence and job performance in call centre environment. sample comprised 135 agents who worked client services, sales administrative environments life insurance company. “Emotional Competency Inventory" that completed by team leaders, used as measuring instrument an overall rating for each participant provided the participating organisation. Results show statistically significant positive...
There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, molecular bases that drive differentiation monocyte-derived DCs (moDCs) towards state are still poorly understood. Here, we studied transcriptional profile moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated monophosphoryl lipid A (MPLA), referred to DM-DCs, an approach identify regulators pathways associated induction properties tolDCs. We...
Type 1 diabetes (T1D) is an autoimmune disorder in which autoreactive T cells destroy insulin-producing β-cells. Interventions that preserve β-cell function represent a fundamental therapeutic goal T1D and biomarkers predict monitor function, changes islet autoantigenic signatures are needed. As proinsulin neoantigens derived from peptides (hybrid insulin peptides, HIPs) important autoantigens, we analysed peripheral blood CD4+ T-cell autoantigen-specific proliferative responses their...
With the advent of novel strategies to induce tolerance in autoimmune and autoimmune-like conditions, clinical trials antigen-specific tolerising immunotherapy have become a reality. Besides safety, it will be essential gather mechanistic data on responding CD4+ T cells order assess effects various immunomodulatory approaches early-phase trials. Peptide-MHCII multimers are an ideal tool for monitoring cell responses unmanipulated directly ex vivo. Various protocols been published but there...
Abstract Aim Protracted bacterial bronchitis (PBB) is a common cause of prolonged cough in young children, and may be precursor bronchiectasis. Bacteria are often present the lower airways both PBB bronchiectasis persistent infections. However, there paucity information available on pathogenesis factors associated with infection progression to This study hypothesised that lung immune cells recurrent differentially express genes related cell dysfunction compared from control subjects. Method...
Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases such as rheumatoid arthritis (RA). Here we characterise monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated monophosphoryl lipid A (MPLA), referred to MPLA-tDCs, in terms gene expression, phenotype, cytokine profile, migratory properties T cell-stimulatory capacity, order explore their suitability cellular therapy. MPLA-tDCs derived displayed an anti-inflammatory...