A5022974460- Salivary Gland Disorders and Functions
- Salivary Gland Tumors Diagnosis and Treatment
- Immune Cell Function and Interaction
- Rheumatoid Arthritis Research and Therapies
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Systemic Sclerosis and Related Diseases
- Diabetes and associated disorders
- Chemokine receptors and signaling
- Galectins and Cancer Biology
- Autoimmune Bullous Skin Diseases
- Growth Hormone and Insulin-like Growth Factors
- Reproductive System and Pregnancy
- Reproductive tract infections research
- Lymphoma Diagnosis and Treatment
- Oral Health Pathology and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Toxin Mechanisms and Immunotoxins
- Glycosylation and Glycoproteins Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
William Harvey Research Institute
2017-2025
Queen Mary University of London
2017-2025
IRCCS Humanitas Research Hospital
2023-2024
University of Milan
2023
Center for Rheumatology
2021
Humanitas University
2013-2020
Centre of Experimental Medicine of the Slovak Academy of Sciences
2020
Istituti di Ricovero e Cura a Carattere Scientifico
2020
University College London
2020
University of London
2020
Accumulation of lactate in the tissue microenvironment is a feature both inflammatory disease and cancer. Here, we assess response immune cells to context chronic inflammation. We report that accumulation inflamed contributes upregulation transporter SLC5A12 by human CD4+ T cells. SLC5A12-mediated uptake into induces reshaping their effector phenotype, resulting increased IL17 production via nuclear PKM2/STAT3 enhanced fatty acid synthesis. It also leads cell retention as consequence reduced...
Primary SS is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels SS-related B-cell lymphoproliferative disorders were studied integrating the results disease activity score and molecular analyses expansion salivary glands.Seventy-six primary (with without manifestations), 56 HCV-related cryoglobulinaemic vasculitis 55 controls studied. s-BLyS...
Objectives To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) B-cell mucosa-associated tissue (MALT) lymphomas (MALT-L) Sjögren’s syndrome (SS) patients. Methods Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across European Union. Transcriptomic (microarray quantitative PCR) analysis, FACS T-cell immunophenotyping intracellular cytokine detection,...
Lymphoma development is the most serious complication of SS and main factor impacting on mortality rate in patients with this condition. Lymphomas are commonly extranodal non-Hodgkin B-cell lymphomas mucosa-associated lymphoid tissue frequently arise salivary glands that target a chronic inflammatory autoimmune process. Extensive work lymphomagenesis has established progression towards lymphoma multistep process related to local antigenic stimulation B cells. These neoplastic cells derived...
Tissue-resident memory cells (Trm) are a subset of T residing persistently and long-term within specific tissues that contribute to persistent inflammation tissue damage. We characterised the phenotype function Trm role CD103 in primary Sjogren's syndrome (pSS).
The polymorphism 158V/F of Fc fragment IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated FCG3A a large cohort RA patients treated with RTX, also by considering possible loss from month +4 +6 after RTX and presence established predictors response.The study analysed 212 patients. European League Against Rheumatism (EULAR) was evaluated at months first infusion. FCGR3A PCR followed Sanger sequencing.The genotypes were associated EULAR...
Objective. The aim of this study was to investigate the biological effects belimumab on B cells in first phase II open-label trial with patients primary SS (pSS) (BELISS). Methods. Peripheral blood cell subsets and their activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry 10 pSS either before or after 24 52 weeks therapy belimumab. Serum BAFF levels ELISA. Results. At baseline, showed a significant increase circulating compared healthy donors matched...
Glucocorticoid (GC)-related adverse events greatly contribute to the outcome in giant cell arteritis (GCA). CYC was investigated as a steroid-sparing agent GCA.Nineteen patients treated with were retrospectively analysed. administered 15 of 19 after failure high doses GC or relapse during medium GC, without MTX, while used ab initio 4 patients, all type 2 diabetes. Follow-up ranged from 1 month nearly 9 years end treatment.The efficacy observed and remission still present 6-12 months...
Autoimmunity is increasingly recognized as a key contributing factor in heart muscle diseases. The functional features of cardiac autoimmunity humans remain undefined because the challenge studying immune responses situ. We previously described subset c-mesenchymal epithelial transition (c-Met)-expressing (c-Met+) memory T lymphocytes that preferentially migrate to tissue mice and humans. In-depth phenotyping peripheral blood cells, including c-Met+ was undertaken groups patients with...
Abstract The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage treatment exposure, we assessed how MerTK relate to histopathology activity, their topographical expression longitudinal modulation by targeted treatments. We show that treatment-naive patients, high AXL levels are associated pauci-immune histology low activity inversely correlate the...
Abstract Several lines of evidence indicate that dopamine (DA) plays a key role in the cross-talk between nervous and immune systems. In this study, we disclose novel immune-regulatory for DA: inhibition effector functions activated NK lymphocytes via selective upregulation D5 dopaminergic receptor response to prolonged cell stimulation with rIL-2. Indeed, engagement D1-like inhibitory following binding DA suppresses proliferation synthesis IFN-γ. The IFN-γ production occurs through blocking...
SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker disease severity. Plasma levels CXCL13 correlate with activity in animal models severity SS, suggesting its potential use surrogate serum marker to monitor local activation. aim this study was evaluate role pathology two independent cohorts.109 patients were...
The development of biologically interpretable and explainable models remains a key challenge in computational pathology, particularly for multistain immunohistochemistry (IHC) analysis. We present BioX-CPath, an graph neural network architecture whole slide image (WSI) classification that leverages both spatial semantic features across multiple stains. At its core, BioX-CPath introduces novel Stain-Aware Attention Pooling (SAAP) module generates meaningful, stain-aware patient embeddings....
Objectives To assess the relationship of circulating and synovial immune cells with molecular pathology disease outcomes in early Rheumatoid Arthritis (RA). Methods Early (<12 months) treatment‐naïve RA patients (n=144) from Pathobiology Cohort (PEAC) were included this posthoc analysis. Following ultrasound‐guided biopsy most active joint, received standard‐of‐care treatment followed up for 12 months. Synovial biopsies analysed by immunohistochemistry classified into pathotypes....
Germinal centre (GC) B cells are pivotal in establishing a robust humoral immune response and long-term serological immunity while maintaining antibody self-tolerance. GC rely on autophagy for antigen presentation homeostatic maintenance. However, these functions, primarily associated with the light zone, cannot explain spatiotemporal upregulation dark zone of GCs. Here, we define functional mechanism controlling chromatin accessibility during their transition. This links nuclear Lamin B1...
Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T -174G/C) have been associated with radiographic severity bone-erosive damage in patients rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography detecting bone erosion. We analyzed the association between TGF-β -174G/C SNPs damage, evaluated by US, a cohort severely active RA. Seventy-seven were enrolled before beginning anti-TNF treatment....
Abstract Immunofibroblasts have been described within tertiary lymphoid structures (TLS) that regulate lymphocyte aggregation at sites of chronic inflammation. Here we report, for the first time, an immunoregulatory property this population, dependent on inducible T-cell co-stimulator ligand and its (ICOS/ICOS-L). During inflammation, immunofibroblasts, alongside other antigen presenting cells, like dendritic cells (DCs), upregulate ICOSL, binding incoming ICOS + T inducing LTα3 production...