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1.

001-es BibID:BIBFORM033526
035-os BibID:PMID:20155824 WOS:000279432400036
Első szerző:Akhmetshina, Alfiya
Cím:Decreased lymphatic vessel counts in patients with systemic sclerosis : association with fingertip ulcers / Alfiya Akhmetshina, Jürgen Beer, Karin Zwerina, Matthias Englbrecht, Katrin Palumbo, Clara Dees, Nicole Reich, Jochen Zwerina, Gabriella Szucs, Johannes Gusinde, Tatiana Nevskaya, Oliver Distler, Dontscho Kerjaschki, Georg Schett, Jörg H. W. Distler
Dátum:2010
ISSN:0004-3591
Megjegyzések:Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc. METHODS: Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age- and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan-endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests. RESULTS: The numbers of podoplanin- and prox-1-positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score. CONCLUSION: These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc. Patients with decreased lymphatic vessel counts may be at particularly high risk of developing fingertip ulcers.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Arthritis and Rheumatism. - 62 : 5 (2010), p. 1513-1522. -
További szerzők:Beer, Jürgen Zwerina, Karin Englbrecht, Matthias Palumbo, Katrin Dees, Clara Reich, Nicole Zwerina, Jochen Szűcs Gabriella (1963-) (belgyógyász, allergológus és klinikai immunológus, reumatológus) Gusinde, Johannes Nevskaya, Tatiana Distler, Oliver Kerjaschki, Dontscho Schett, Georg Distler, Jörg H. W.
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2.

001-es BibID:BIBFORM015816
Első szerző:Gerlag, Danielle M.
Cím:Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate / Gerlag, D. M., Hollis, S., Layton, M., Vencovsky, J., Szekanecz, Z., Braddock, M., Tak, P. P., The ESCAPE Study Group
Dátum:2010
ISSN:1529-0131 (Electronic)
Megjegyzések:To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. METHODS: Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were performed, including studies of ligand binding and chemotaxis. The pharmacokinetics of AZD5672 were assessed in both single- and multiple-dose studies in healthy volunteers. A randomized, placebo-controlled, phase IIb study was conducted in patients with active RA receiving methotrexate. Treatment arms were AZD5672 (20, 50, 100, or 150 mg orally, once daily), matched placebo, or open-label etanercept (50 mg subcutaneously, once weekly). The primary end point was the proportion of patients achieving a 20% improvement response on the American College of Rheumatology improvement criteria (ACR20) at week 12. Secondary end points included the ACR20 over time, as well as 50% (ACR50) and 70% (ACR70) improvement responses, changes in individual components of the ACR improvement criteria, and disease activity measured with the Disease Activity Score based on the 28-joint count. RESULTS: AZD5672 was a highly potent and selective antagonist of CCR5, displaying nonproportional steady-state pharmacokinetics while inhibiting internalization of CCR5 in an ex vivo macrophage inflammatory protein 1beta stimulation assay in which AZD5672 was evaluated over the 20-150-mg dose range. In the phase IIb study testing this dose range in patients with RA (n = 371 patients randomized to received treatment), AZD5672 was generally well tolerated, with no unexpected adverse events. There was no statistically significant difference in the proportion of patients achieving an ACR20 response at week 12 between those receiving any dose of AZD5672 and those receiving placebo; etanercept was significantly more efficacious than AZD5672 and placebo. CONCLUSION: Despite a clear rationale for targeting CCR5, this clinical study showed that AZD5672, administered orally, did not have any clinical benefit, suggesting that CCR5 antagonism alone is unlikely to be a viable therapeutic strategy in RA.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Antirheumatic Agents/therapeutic use
Arthritis, Rheumatoid/*drug therapy
Benzeneacetamides/*therapeutic use
Chi-Square Distribution
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Male
Methotrexate/*therapeutic use
Receptors, CCR5/*antagonists & inhibitors
Sulfonamides/*therapeutic use
Treatment Outcome
Megjelenés:Arthritis and Rheumatism. - 62 : 11 (2010), p. 3154-3160. -
További szerzők:Hollis, Sally Layton, Mark Vencovsky, Jiri Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Braddock, Martin Tak, Paul P. The ESCAPE Study Group
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3.

001-es BibID:BIBFORM050381
035-os BibID:PMID:23653330
Első szerző:Glant Tibor T.
Cím:Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models / Tibor T. Glant, Timea Besenyei, András Kádár, Júlia Kurkó, Beata Tryniszewska, János Gál, Györgyi Soós, Zoltán Szekanecz, Gyula Hoffmann, Joel A. Block, Robert S. Katz, Katalin Mikecz, Tibor A. Rauch
Dátum:2013
ISSN:0004-3591
Megjegyzések:To identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA), and to explore the therapeutic potential of the targeted inhibition of these factors. METHODS: Polymerase chain reaction (PCR) arrays were used to investigate the expression profile of genes that encode key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative reverse transcription-PCR, Western blot, and flow cytometry methods. The targeted inhibition of the up-regulated enzymes was studied in arthritic mice. RESULTS: A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinases A and B, both of which were highly expressed in arthritic mice and treatment-naive RA patients, were selected for detailed analysis. Elevated aurora kinase expression was accompanied by increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against disease onset, and attenuated inflammatory reactions in arthritic mice. CONCLUSION: Arthritis development is accompanied by changes in expression of a number of epigenome-modifying enzymes. Drug-induced down-regulation of the aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target aurora kinases can potentially improve RA management.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
epigenome modifiers
rheumatoid arthritis
Megjelenés:Arthritis and Rheumatism. - 65 : 7 (2013), p. 1725-1735. -
További szerzők:Besenyei Tímea (1980-) (reumatológus, belgyógyász) Kádár András (1977-) (belgyógyász) Kurkó Júlia Emese (1979-) (reumatológus) Tryniszewska Beáta Gál János Soós Györgyike (1959-) (pathológus) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Hoffmann Gyula Block, Joel A. Katz, Robert S. Mikecz Katalin Rauch Tibor A.
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4.

001-es BibID:BIBFORM039164
Első szerző:Glant Tibor T.
Cím:Cartilage-specific constitutive expression of TSG-6 protein (product of tumor necrosis factor alpha-stimulated gene 6) provides a chondroprotective, but not antiinflammatory, effect in antigen-induced arthritis / Glant, T. T., Kamath, R. V., Bardos, T., Gal, I., Szanto, S., Murad, Y. M., Sandy, J. D., Mort, J. S., Roughley, P. J., Mikecz, K.
Dátum:2002
ISSN:0004-3591
Megjegyzések:To study the chondroprotective effect of constitutively expressed TSG-6 protein (tumor necrosis factor alpha-induced protein 6; Tnfip6) in cartilage, using antigen-induced arthritis (AIA) in mice. METHODS: Transgenic mice constitutively expressing TSG-6 protein in cartilage were generated. Cartilage-specific constitutive expression of TSG-6 protein was confirmed by in situ hybridization, Western blot analysis, and immunohistochemistry. Control and transgenic mice were immunized with methylated bovine serum albumin (mBSA), and arthritis was induced by the intraarticular injection of mBSA. Mice were monitored up to day 35 after the challenge, and knee joint sections were examined for loss of cartilage proteoglycan (aggrecan) using Safranin O staining and antibodies to neoepitopes generated by various metalloproteinases (MPs). The loss of aggrecan in Safranin O-stained sections was quantified by morphometric methods. RESULTS: Tsg6/tnfip6 transgenic mice constitutively expressed tsg6/tnfip6 messenger RNA and corresponding TSG-6 protein in cartilage from embryonic life through adulthood, without any phenotypic abnormalities. These mice were used for AIA studies. Intraarticular injection of mBSA uniformly induced severe inflammation both in control (wild-type and an irrelevant transgenic line) mice and in tsg6/tnfip6 transgenic mice. In contrast to the mBSA-injected knee joints of control animals that were heavily damaged from day 5, the cartilage of transgenic mice that constitutively expressed TSG-6 protein remained intact for at least 1 week, and this was followed by a relatively reduced loss of aggrecan. Concomitant with the loss of aggrecan, MP-generated neoepitopes accumulated in unprotected joints. By day 35, the proteoglycan content returned to nearly normal levels in tsg6/tnfip6 transgenic mice, whereas it remained low in MP-damaged knee cartilage of control mice. CONCLUSION: TSG-6 protein is known to form a complex with inter-alpha-inhibitor (IalphaI), a potent serine protease inhibitor, which may be immobilized via the hyaluronan (HA)-binding domain of TSG-6 protein in the HA-rich extracellular matrix of cartilage. Thus, the local accumulation of TSG-6 protein and TSG-6 protein-bound IalphaI in tsg6/tnfip6 transgenic mice may inhibit serine proteases and subsequent activation of MPs. It is suggested that this mechanism might protect cartilage from extensive degradation even in the presence of acute inflammation.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Arthritis And Rheumatism. - 46 : 8 (2002), p. 2207-2218. -
További szerzők:Kamath, Rajesh V. Bárdos Tamás Gál István (1957-) (belgyógyász) Szántó Sándor (1968-) (belgyógyász, reumatológus) Murad, Yanal M. Sandy, John D. Mort, John S. Roughley, Peter J. Mikecz Katalin
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5.

001-es BibID:BIBFORM046530
Első szerző:Hanyecz Anita
Cím:Achievement of a synergistic adjuvant effect on arthritis induction by activation of innate immunity and forcing the immune response toward the Th1 phenotype / Hanyecz, A., Berlo, S. E., Szanto, S., Broeren, C. P., Mikecz, K., Glant, T. T.
Dátum:2004
ISSN:0004-3591
Megjegyzések:To apply and analyze the mechanisms of action of dimethyldioctadecylammonium bromide (DDA), a powerful adjuvant that does not have the side effects of the conventionally used Freund's adjuvants, in proteoglycan-induced arthritis (PGIA) and collagen-induced arthritis (CIA). METHODS: PGIA and CIA were generated using standard immunization protocols with cartilage proteoglycan aggrecan (PG) or human type II collagen (CII) emulsified with Freund's complete adjuvant (CFA), and compared with PGIA and CIA generated using immunization protocols in which the same antigens were used in combination with the adjuvant DDA. Immune responses to immunizing and self PGs and CII, and the incidence, severity, and onset of arthritis were monitored throughout the experiments. In addition, a new, inexpensive, and powerful method of inducing arthritis using crude cartilage extracts is described. RESULTS: A significantly reduced onset period and a more severe arthritis were achieved in BALB/c mice immunized with cartilage PGs in DDA. PGs from bovine, ovine, and porcine cartilage, which otherwise have no effect or have only a subarthritogenic effect, and crude extracts of human osteoarthritic cartilage induced a 100% incidence with a very high arthritis score in BALB/c mice. The overall immune responses to either CII or PG were similar in antigen/CFA-immunized and antigen/DDA-immunized animals, but the Th1/Th2 balance shifted significantly toward a Th1 bias in DDA-injected animals with either PGIA or CIA. CONCLUSION: DDA, which was first used in autoimmune models, is a potent nonirritant adjuvant, which eliminates all undesired side effects of the Freund's adjuvants. DDA exerts a strong stimulatory effect via the activation of nonspecific (innate) immunity and forces the immune regulation toward Th1 dominance. These lines of evidence also suggest the possibility that seemingly innocuous compounds may exert an adjuvant effect in humans and may create the pathophysiologic basis of autoimmunity in susceptible individuals via the activation/stimulation of innate immunity.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Arthritis And Rheumatism. - 50 : 5 (2004), p. 1665-1676. -
További szerzők:Berlo, Suzanne E. Szántó Sándor (1968-) (belgyógyász, reumatológus) Broeren, Chris P. M. Mikecz Katalin Glant Tibor T.
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6.

001-es BibID:BIBFORM105027
035-os BibID:(cikkazonosító)152109 (WoS)001042945400005 (Scopus)85140434684
Első szerző:Hartman, Linda
Cím:Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+ : the pragmatic, multicenter, placebo-controlled GLORIA trial / L. Hartman, M. El Alili, M. Cutolo, D. Opris, J. A. P. Da Silva, Z. Szekanecz, F. Buttgereit, P. Masaryk, R. Bos, M. R. Kok, S. Paolino, V. M. H. Coupè, W. F. Lems, M. Boers, GLORIA consortium
Dátum:2022
ISSN:0049-0172
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Seminars In Arthritis And Rheumatism. - 57 (2022), p. 1-8. -
További szerzők:El Alili, M. Cutolo, Maurizio Opris, Daniela (1976-) (reumatológus) Da Silva, J. A. P. Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Buttgereit, Frank Masaryk, Pavol Bos, Reinhard Kok, Marc R. Paolino, Sabrina Coupé, V. M. H. Lems, Willem F. Boers, Maarten GLORIA Trial consortium
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7.

001-es BibID:BIBFORM072682
Első szerző:Hudson, Marie
Cím:Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis : results from the International Scleroderma Renal Crisis Survey / Hudson Marie, Baron Murray, Tatibouet Solène, Furst Daniel E., Khanna Dinesh, International Scleroderma Renal Crisis Study Investigators
Dátum:2014
ISSN:0049-0172
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
scleroderma renal crisis
Megjelenés:Seminars In Arthritis And Rheumatism. - 43 : 5 (2014), p. 666-672. -
További szerzők:Baron, Murray Tatibouet, Solène Furst, Daniel E. Khanna, Dinesh Szűcs Gabriella (1963-) (belgyógyász, allergológus és klinikai immunológus, reumatológus) International Scleroderma Renal Crisis Study Investigators
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8.

001-es BibID:BIBFORM033048
Első szerző:Kerekes György (belgyógyász, kardiológus, angiológus)
Cím:Adalimumab improves endothelial function and microcirculation in rheumatoid arthritisas determined by simultaneous assessment of brachial artery flow-mediated vasodilation and laser doppler flowmetry / György Kerekes, Vanda Pongrácz, Szilvia Szamosi, Gabriella Szücs, Andrea Váncsa, Orsolya Tímár, Zoltán Csiki, Edit Végh, Pál Soltész, Zoltan Szekanecz
Dátum:2011
ISSN:0004-3591
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
Megjelenés:Arthritis and rheumatism. - 63 : 10 (2011), p. S74. -
További szerzők:Pongrácz Vanda Szamosi Szilvia (1975-) (belgyógyász, reumatológus) Szűcs Gabriella (1963-) (belgyógyász, allergológus és klinikai immunológus, reumatológus) Váncsa Andrea (1972-) (orvos) Tímár Orsolya (1980-) (belgyógyász) Csiki Zoltán (1962-) (belgyógyász, allergológus, klinikai immunológus, reumatológus) Végh Edit (1978-) (reumatológus, belgyógyász) Soltész Pál (1961-) (belgyógyász, kardiológus) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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9.

001-es BibID:BIBFORM035348
Első szerző:Lakos Gabriella (laboratóriumi szakorvos, transzfúziológus, immunológus)
Cím:Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis : association with disease duration, rheumatoid factor production and the presence of the shared epitope / Gabriella Lakos, Lilla Soós, Andrea Fekete, Zoltán Szabó, Margit Zeher, Ildikó F. Horváth, Katalin Dankó, Anikó Kapitány, Ágnes Gyetvai, Gyula Szegedi, Zoltán Szekanecz
Dátum:2007
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
egyetemen (Magyarországon) készült közlemény
Megjelenés:Arthritis and Rheumatism. Supplement. - 56 : 9 (2007), p. S438. -
További szerzők:Soós Lilla Fekete Andrea (immunológus) Szabó Zoltán (1970-) (belgyógyász, reumatológus) Zeher Margit (1957-2018) (belgyógyász, allergológus és klinikai immunológus, reumatológus) Horváth Ildikó Fanny (1980-) (belgyógyász, allergológus, klinikai immunológus) Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Kapitány Anikó (1979-) (molekuláris biológus) Gyetvai Ágnes Szegedi Gyula (1936-2013) (belgyógyász, immunológus) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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10.

001-es BibID:BIBFORM007088
Első szerző:Szabó Zoltán (belgyógyász, reumatológus)
Cím:Genetic control of experimental spondylarthropathy / Szabo, Z., Szanto, S., Vegvari, A., Szekanecz, Z., Mikecz, K., Glant, T. T.
Dátum:2005
ISSN:0004-3591 (Print)
Megjegyzések:To characterize experimentally induced spondylarthropathy (SpA) in arthritis-susceptible inbred mice and in their F(1) and F(2) hybrid generations of susceptible and resistant mouse strains. METHODS: SpA was induced in susceptible BALB/c and C3H/HeJCr (C3H) strains of mice, and in their F(1) and F(2) generations derived from intercrosses with arthritis- and/or spondylitis-resistant DBA/2 and DBA/1 parent strains, by systemic immunization with cartilage proteoglycan (PG) aggrecan. The incidence and severity of PG-induced spondylitis (PGIS) were scored histologically, and these scores for spine involvement were correlated with serum antibody and cytokine levels and with in vitro T cell responses to cartilage PG. RESULTS: PGIS was induced by systemic immunization with cartilage PG in adjuvant, and approximately 60-70% of susceptible mouse strains and their F(2) hybrids developed spondylitis either with or without arthritis. Adjuvants, particularly those activating the innate immune system and enforcing the Th1 dominance, had significant effects on the outcome and progression of SpA. The DBA/1 strain appeared to carry genes protecting this strain and its F(1) and F(2) hybrids from spondylitis, whereas the DBA/2 strain, although resistant to PGIS, harbored genes permitting PGIS in its hybrid generations. Arthritis- and/or spondylitis-susceptible BALB/c and C3H parent strains and their F(2) hybrids exhibited the highest incidence and severity of spondylitis. CONCLUSION: PGIS, a murine model of autoimmune spondylitis, shows similarities to ankylosing spondylitis. Segregation of susceptibility to PG-induced arthritis (PGIA) from that to PGIS in different genetic crosses suggests that PGIA and PGIS are separate diseases. Therefore, this model allows for the elucidation of genetic components involved in the etiology of SpA, independent of those controlling the susceptibility to PGIA.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Aggrecans
Animals
Arthritis
Extracellular Matrix Proteins
Female
Genetic Predisposition to Disease
Hybridization, Genetic
Incidence
Lectins, C-Type
Male
Mice
Mice, Inbred Strains
Proteoglycans
Severity of Illness Index
Species Specificity
Spondylarthropathies
Megjelenés:Arthritis and Rheumatism. - 52 : 8 (2005), p. 2452-2460. -
További szerzők:Szántó Sándor (1968-) (belgyógyász, reumatológus) Végvári Anikó (belgyógyász, III. sz. Belgyógyászati Klinika) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Mikecz Katalin Glant Tibor T.
Internet cím:elektronikus változat
DOI
elektronikus változat
Borító:

11.

001-es BibID:BIBFORM046531
Első szerző:Szántó Sándor (belgyógyász, reumatológus)
Cím:Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice / Sándor Szántó, Tamás Bárdos, István Gál, Tibor T. Glant, Katalin Mikecz
Dátum:2004
ISSN:0004-3591
Megjegyzések:OBJECTIVE: To gain insight into the mechanisms of the antiinflammatory effect of tumor necrosis factor alpha (TNFalpha)-induced protein 6 (Tnfip6) in arthritis, using Tnfip6-deficient animals. METHODS: TNFalpha-stimulated gene 6 (TSG-6) coding for Tnfip6 was disrupted. Tnfip6-deficient mice were backcrossed into proteoglycan-induced arthritis (PGIA)-susceptible BALB/c mice, and arthritis was induced by systemic immunization with cartilage proteoglycan (PG). Thioglycollate-induced sterile peritonitis was also assessed, to monitor the early events of neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence or absence of treatment with recombinant murine Tnfip6. RESULTS: The onset of PGIA was similar, but progression and severity were significantly greater, in Tnfip6-deficient mice compared with wild-type BALB/c mice. However, this was not associated with enhanced T or B cell responses to cartilage PGs, but rather, an early and more extensive infiltration of the synovium with neutrophil leukocytes was the most prominent histopathologic feature of PGIA in Tnfip6-deficient mice. This was accompanied by elevated serum levels of interleukin-6 and amyloid A, and significantly increased activities of the enzymes plasmin, myeloperoxidase, and neutrophil elastase in the inflamed paw joints of Tnfip6-null mice, when compared with that of the wild-type littermates. Loss of control over several components of inflammation resulted in extensive and rapid cartilage degradation, bone erosion, joint ankylosis, and deformities in Tnfip6-null animals. In support of the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was dramatically suppressed by intravenous injection of recombinant murine Tnfip6. CONCLUSION: Tnfip6 is a multifunctional antiinflammatory protein that is produced at the site of inflammation and can be retained by the hyaluronan-rich extracellular matrix. A major effect of Tnfip6 is the inhibition of the extravasation of PMN cells, predominantly neutrophils, into the site of inflammation, most likely via a CD44/hyaluronan/Tnfip6-mediated blocking mechanism.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Arthritis And Rheumatism. - 50 : 9 (2004), p. 3012-3022. -
További szerzők:Bárdos Tamás Gál István (1957-) (belgyógyász) Glant Tibor T. Mikecz Katalin
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12.

001-es BibID:BIBFORM046532
Első szerző:Szántó Sándor (belgyógyász, reumatológus)
Cím: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 / Sándor Szántó, Tamás Bárdos, Zoltán Szabó, Chella S. David, Edit I. Buzás, Katalin Mikecz, Tibor T. Glant
Dátum:2004
ISSN:0004-3591
Megjegyzések:OBJECTIVE: To determine whether the rheumatoid arthritis (RA)-predisposing class II molecules of the major histocompatibility complex (MHC) can present cartilage proteoglycan (PG) aggrecan, and if so, to determine the epitope repertoire of the human cartilage PG in HLA-transgenic mice and determine whether HLA-transgenic mice develop arthritis in response to immunization with human cartilage PG. METHODS: Mice transgenic for HLA-DR2.Ab(0), DR3.Ab(0), DR4.Ab(0), and DQ8.Ab(0), lacking their own (mouse) class II antigens (Ab(0)), on the original (arthritis-resistant) and the arthritis-susceptible BALB/c backgrounds, were immunized with human cartilage PG. The T cell epitope repertoire presented by these class II MHC alleles was determined using a synthetic peptide library (143 peptides of the core protein of human cartilage PG), and arthritis development was monitored and compared in wild-type and HLA-transgenic/congenic BALB/c mice. RESULTS: Mice of the 4 HLA-transgenic lines, either on the original mixed, arthritis-resistant background or DR4.Ab(0)- and DQ8.Ab(0)-transgenic/congenic mice on the arthritis-susceptible BALB/c genetic background, responded well to PG immunization (as assessed by T cell responses and antibody and cytokine production), and a number of T cell epitopes along the core protein of human cartilage PG were identified. DR4.Ab(0)- and DQ8.Ab(0)-transgenic mice immunized with human cartilage PG developed arthritis, but only when these class II MHC molecules were present on the arthritis-susceptible (BALB/c) genetic background. CONCLUSION: A number of human cartilage PG epitopes can be presented by HLA alleles that predispose to the development of RA, but the epitopes of the cartilage PG presented by HLA-DR4 or HLA-DQ8 can induce arthritis only in the presence of an appropriate genetic (non-MHC) background.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Arthritis And Rheumatism. - 50 : 6 (2004), p. 1984-1995. -
További szerzők:Bárdos Tamás Szabó Zoltán (1970-) (belgyógyász, reumatológus) David, Chella S. Buzás Edit Mikecz Katalin Glant Tibor T.
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