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One or more keywords matched the following properties of Glant, Tibor
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overview Originally as a physician, after spending three years in full-time research (Joint Diseases Laboratories, Shriners Hospital, Montreal, Canada and NIH/NIDR Bethesda), I have fundamentally changed my career converting my clinical experience and training to biomedical science. My major research interest during the past 30 years has been autoimmunity and autoimmune regulation of T and B cells in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and its corresponding animal models. I have generated monoclonal antibodies (mAbs) to cartilage antigenic components, and used these mAbs for immuno-electron microscopic localization of cartilage matrix molecules in aging and diseased cartilages. During the production of mAbs, serendipitously, I (and my immediate colleagues) “discovered” cartilage proteoglycan (PG) aggrecan-induced arthritis (PGIA) in genetically susceptible (arthritis-prone) BALB/c mice. I have had a long-standing interest and commitment to training of medical students for histopathology, and later on scientists and physician-scientists. In addition to mentoring pre- and postdoctoral trainees in my laboratory and faculty members, I was PI of numerous R01, P01 and R21 NIH grants; I was always funded since I moved to the USA. My early research was thymosin-producing epithelioid cells expected to control early T cell selection in mouse embryos and the mechanisms of Wasting syndrome. Simultaneously, I studied cartilage and bone development as well as cartilage repair and bone healing in animal models, and immunogenicity/antigenicity of cartilage and bone non-collagenous macromolecules. This included numerous histochemistry (mostly enzyme and immune histochemistry), biochemical and immunological methods. I was the first to localize proteoglycan (PG) aggrecan and link protein by immune electron microscopy in cartilage tissue, and first described the autoimmune potential of cartilage PG in patients with RA or ankylosing spondylitis. I/we have sequenced the core proteins of mouse and canine cartilage PG aggrecans, and described splice variants of human PG aggrecan. These pioneer studies were repeated and extended in many laboratories. My expertise in bone and cartilage biochemistry and biology was beneficial when I/we have studied the mechanism of aseptic loosening of total joint replacements, which studies then changed the orthopedic term/diagnosis from “cement disease” to “particulate disease”. Submicron-sized wear debris/particulates are phagocytized by macrophages, fibroblasts and osteoblast, trigger these cells to secrete pro-inflammatory cytokines and proteolytic enzymes leading to aseptic bone resorption and loosening of prosthetic device. After I/we described the PG (aggrecan)-induced arthritis (PGIA) in BALB/c mice in 1987, a large number of studies focused on the immune pathomechanism of this model of RA and mapping studies of (auto)epitopes. PGIA model shares similarities with RA as indicated by clinical assessments, laboratory tests, and histopathology of diarthrodial joints. The development of the disease in genetically susceptible mice is based upon the development of cross-reactive immune responses between the immunizing (human) and self (mouse) cartilage PG. The recessive inheritance of disease susceptibility, as in RA, is dictated by both MHC- and non-MHC-associated genes. I/we identified dominant (arthritic) and subdominant epitopes of human and mouse (self) PG, tested the arthritogenic potential of human cartilage PG, and I generated recombinant human G1 domain (a globular domain of PG which carry all arthritogenic epitopes. This model was used to test the efficacy of Leflunomide (component 418). Numerous laboratories use the PGIA model all over the world, and human studies led to the identification of citrullinated PG epitopes in RA patients. A fourth and most recent research direction is the genetic and epigenetic alterations in PGIA model and in RA patients. I/we identified over 25 quantitative trait loci (QTLs) in different genetic combination of F2 mice. A special select direction of these genetic studies was to generate congenic mice (a short resistant DBA2 allele in susceptible BALB/c background). These congenic mice were/are tested for arthritis susceptibility; genomic regions sequenced and mutated genes selected for in vitro and in vivo studies. Eight of these 25 QTL are syntenic with RA genomic risk loci. From these 8 overlapping RA risk loci we have selected mouse chromosomes 2 and 3, which are highly susceptible to arthritis and syntenic with human chromosomes 9 and 1. Mouse/human susceptible regions carry the PTPN22 (mChr3/hChr1) and C5/TRAF1/PHF19 (mChr2/hChr9) RA risk alleles. The mutated genes are studied in vitro and generating and testing gene-deficient mice for arthritis in susceptible BALB/c background, and allele-specific transgenic mice to rescue the gene deficiency-induced defect(s). My Scopus API key: 458a8af4ddad17c0c313a5e8b8454348 My Orcid ID: https://orcid.org/0000-0002-1706-3820 MY NIH COMMONS: TGLANT Research Areas: Autoimmunity, Rheumatoid Arthritis, Ankylosing Spondylitis, Genetics, Periprosthetic osteolysis My Faculty Profile at Rush University Medical Center: https://www.rushu.rush.edu/faculty/tibor-t-glant-md-phd Education: MD, University of Medical School (DOTE) Debrecen, Hungary PhD, University of Medical School (DOTE) Debrecen, Hungary DMsc. Hungarian Academy of Sciences, Budapest, Hungary
One or more keywords matched the following items that are connected to Glant, Tibor
Item TypeName
Concept Chondroitin Sulfate Proteoglycans
Concept Proteoglycans
Academic Article The localization of proteoglycans and glycoproteins in the hyaline cartilage.
Academic Article Antigenicity of bone tissue. I. Immunological and immunohistochemical study of non-collagenous proteins of the bovine cortical bone.
Academic Article Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide.
Academic Article Serum keratan sulfate--a marker of predisposition to polyarticular osteoarthritis.
Academic Article Cartilage proteoglycan-induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis.
Academic Article Epitopes of cartilage core proteins and GAG pattern in human non-Hodgkin lymphoma xenografts.
Academic Article Chondrons from articular cartilage. (IV). Immunolocalization of proteoglycan epitopes in isolated canine tibial chondrons.
Academic Article Circulating keratan sulfate: a marker of cartilage proteoglycan catabolism in osteoarthritis.
Academic Article Proteoglycan-specific autoreactive antibodies and T-lymphocytes in experimental arthritis and human rheumatoid joint diseases.
Academic Article Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice.
Academic Article Proteoglycan-targeted antibodies as markers on non-Hodgkin lymphoma xenografts.
Academic Article Monoclonal antibodies to different protein-related epitopes of human articular cartilage proteoglycans.
Academic Article Age-related changes in protein-related epitopes of human articular-cartilage proteoglycans.
Academic Article Proteoglycan epitopes as potential markers of normal and pathologic cartilage metabolism.
Academic Article Isolation of proteoglycan-specific T lymphocytes from patients with ankylosing spondylitis.
Academic Article The structure and abundance of cartilage proteoglycans during early development of the human fetus.
Academic Article Cartilage proteoglycans as potential autoantigens in humans and in experimental animals.
Academic Article The identification and characterization of two populations of aggregating proteoglycans of high buoyant density isolated from post-natal human articular cartilages of different ages.
Academic Article Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan.
Academic Article Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology.
Academic Article Induction of cartilage degradation in experimental arthritis produced by allogeneic and xenogeneic proteoglycan antigens.
Academic Article Localization of antigenic components in proteoglycan aggregate of bovine nasal cartilage.
Academic Article Concanavalin A-binding link protein in the proteoglycan aggregate of hyaline cartilage.
Academic Article Experimental arthritis produced by proteoglycan antigens in rabbits.
Academic Article VDIPEN, a metalloproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis.
Academic Article Mapping of arthritogenic/autoimmune epitopes of cartilage aggrecans in proteoglycan-induced arthritis.
Academic Article Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage.
Academic Article A proteoglycan (aggrecan)-specific T cell hybridoma induces arthritis in BALB/c mice.
Academic Article Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis.
Academic Article Interferon-gamma but not granulocyte/macrophage colony-stimulating factor augments proteoglycan presentation by synovial cells and chondrocytes to an autopathogenic T cell hybridoma.
Academic Article Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis.
Academic Article Presentation of cartilage proteoglycan to a T cell hybridoma derived from a mouse with proteoglycan-induced arthritis.
Academic Article Complete coding sequence, deduced primary structure, chromosomal localization, and structural analysis of murine aggrecan.
Academic Article Mediators and autopathogenic effector cells in proteoglycan-induced arthritic and clinically asymptomatic BALB/c mice.
Academic Article Migration and homing of lymphocytes to lymphoid and synovial tissues in proteoglycan-induced murine arthritis.
Academic Article Differentiation antigens of human articular chondrocytes and their tissue distribution as assessed by monoclonal antibodies.
Academic Article Effect of pregnancy on proteoglycan-induced progressive polyarthritis in BALB/c mice: remission of disease activity.
Academic Article Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module.
Academic Article Substrate specificity of 'elastomucoproteinase': an enzyme which can degrade cartilage aggrecan.
Academic Article Functional assessment of joint use in experimental inflammatory murine arthritis.
Academic Article Species-specific alternative splicing of the epidermal growth factor-like domain 1 of cartilage aggrecan.
Academic Article Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples.
Academic Article Immunopathologic role of proteoglycan antigens in rheumatoid joint disease.
Academic Article Critical roles of glycosaminoglycan side chains of cartilage proteoglycan (aggrecan) in antigen recognition and presentation.
Academic Article Progressive polyarthritis induced in BALB/c mice by aggrecan from normal and osteoarthritic human cartilage.
Academic Article Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.
Academic Article Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.
Academic Article A genome scan using a novel genetic cross identifies new susceptibility loci and traits in a mouse model of rheumatoid arthritis.
Academic Article Variations in susceptibility to proteoglycan-induced arthritis and spondylitis among C3H substrains of mice: evidence of genetically acquired resistance to autoimmune disease.
Academic Article Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis.
Academic Article Anti-inflammatory and chondroprotective effect of TSG-6 (tumor necrosis factor-alpha-stimulated gene-6) in murine models of experimental arthritis.
Academic Article Th1 and Th2 cytokines regulate proteoglycan-specific autoantibody isotypes and arthritis.
Academic Article Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice.
Academic Article Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci.
Academic Article TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage.
Academic Article Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency.
Academic Article Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels.
Academic Article Differential recognition of altered peptide ligands distinguishes two functionally discordant (arthritogenic and nonarthritogenic) autoreactive T cell hybridoma clones.
Academic Article Induction of arthritis in SCID mice by T cells specific for the "shared epitope" sequence in the G3 domain of human cartilage proteoglycan.
Academic Article Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics.
Academic Article Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis.
Academic Article Induction of arthritis in HLA-DR4-humanized and HLA-DQ8-humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non-MHC) genetic background.
Academic Article Proteoglycan aggrecan-induced arthritis: a murine autoimmune model of rheumatoid arthritis.
Academic Article Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice.
Academic Article A longitudinal study on an autoimmune murine model of ankylosing spondylitis.
Academic Article Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation.
Academic Article Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis.
Academic Article Genetic control of experimental spondylarthropathy.
Academic Article Two major interacting chromosome loci control disease susceptibility in murine model of spondyloarthropathy.
Academic Article T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
Academic Article Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan.
Academic Article Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation.
Academic Article Experimental spondyloarthropathies: animal models of ankylosing spondylitis.
Academic Article Expression of CD44 and L-selectin in the innate immune system is required for severe joint inflammation in the proteoglycan-induced murine model of rheumatoid arthritis.
Academic Article Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice.
Academic Article Interleukin-4 regulates proteoglycan-induced arthritis by specifically suppressing the innate immune response.
Academic Article Two loci on chromosome 15 control experimentally induced arthritis through the differential regulation of IL-6 and lymphocyte proliferation.
Academic Article Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation.
Academic Article Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis.
Academic Article IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis.
Academic Article Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis.
Academic Article BALB/c mice genetically susceptible to proteoglycan-induced arthritis and spondylitis show colony-dependent differences in disease penetrance.
Academic Article The genetic background of ankylosing spondylitis.
Academic Article IFN-gamma regulates the requirement for IL-17 in proteoglycan-induced arthritis.
Academic Article Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints.
Academic Article Impaired activation-induced cell death promotes spontaneous arthritis in antigen (cartilage proteoglycan)-specific T cell receptor-transgenic mice.
Academic Article Animals lacking link protein have attenuated perineuronal nets and persistent plasticity.
Academic Article Proteoglycan-induced arthritis and recombinant human proteoglycan aggrecan G1 domain-induced arthritis in BALB/c mice resembling two subtypes of rheumatoid arthritis.
Academic Article B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis.
Academic Article T cell receptor (TCR) signal strength controls arthritis severity in proteoglycan-specific TCR transgenic mice.
Academic Article Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis.
Academic Article In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis.
Academic Article Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors.
Academic Article The role of citrullination of an immunodominant proteoglycan (PG) aggrecan T cell epitope in BALB/c mice with PG-induced arthritis.
Academic Article Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis.
Academic Article Brief report: Autologous stem cell transplantation restores immune tolerance in experimental arthritis by renewal and modulation of the Teff cell compartment.
Academic Article Proteoglycan aggrecan conducting T cell activation and apoptosis in a murine model of rheumatoid arthritis.
Academic Article Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cells generated in vitro from murine bone marrow.
Academic Article Characterization and Localization of Citrullinated Proteoglycan Aggrecan in Human Articular Cartilage.
Academic Article Immune Recognition of Citrullinated Proteoglycan Aggrecan Epitopes in Mice with Proteoglycan-Induced Arthritis and in Patients with Rheumatoid Arthritis.
Academic Article Immunoregulation of Proteoglycan-Induced Arthritis in Balb/c Mice.
Academic Article Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis.
Academic Article Regulatory role of capsaicin-sensitive peptidergic sensory nerves in the proteoglycan-induced autoimmune arthritis model of the mouse.
Academic Article Vaccination by Two DerG LEAPS Conjugates Incorporating Distinct Proteoglycan (PG, Aggrecan) Epitopes Provides Therapy by Different Immune Mechanisms in a Mouse Model of Rheumatoid Arthritis.
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