TY - JOUR AU - Soos, Boglarka AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, Edit AU - Szamosi, Szilvia AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Kerekes, György AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Christians, Uwe AU - Klawitter, Jelena AU - Seres, Tamas AU - Szekanecz, Zoltán TI - Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 9 PY - 2022 PG - 16 SN - 2296-858X DO - 10.3389/fmed.2022.1011734 UR - https://m2.mtmt.hu/api/publication/33457576 ID - 33457576 N1 - Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Intensive Care Unit, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Export Date: 4 January 2023 Correspondence Address: Szekanecz, Z.; Department of Rheumatology, Hungary; email: szekanecz.zoltan@med.unideb.hu AB - IntroductionRheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Materials and methodsThirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. ResultsTwenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. ConclusionOne-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study. LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Hascsi, Zsolt AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, Edit AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Soós, Boglárka AU - Kerekes, György AU - Szekanecz, Éva AU - Hódosi, Katalin AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Seres, Tamás AU - Szekanecz, Zoltán AU - Szamosi, Szilvia TI - Prospective, simultaneous assessment of joint and vascular inflammation by PET/CT in tofacitinib-treated patients with rheumatoid arthritis: associations with vascular and bone status JF - RMD OPEN J2 - RMD OPEN VL - 7 PY - 2021 IS - 3 SP - 1 EP - 10 PG - 10 SN - 2056-5933 DO - 10.1136/rmdopen-2021-001804 UR - https://m2.mtmt.hu/api/publication/32575467 ID - 32575467 N1 - 325871 LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Hascsi, Z. AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Vegh, E. AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Soos, B. AU - Kerekes, György AU - Szekanecz, Éva AU - Hodosi, K. AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Seres, T. AU - Szekanecz, Zoltán AU - Szamosi, Szilvia TI - SIMULTANEOUS ASSESSMENT OF JOINT AND VASCULAR INFLAMMATION BY PET-CT IN TOFACITINIB-TREATED PATIENTS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 80 PY - 2021 SP - 425 EP - 425 PG - 1 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-eular.2473 UR - https://m2.mtmt.hu/api/publication/32501310 ID - 32501310 N1 - 334210 LA - English DB - MTMT ER - TY - JOUR AU - Soos, B. AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Vegh, E. AU - Szamosi, Szilvia AU - Pethő, Zsófia AU - Gulyás, Katalin AU - Kerekes, György AU - Szekanecz, Éva AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Christians, U. AU - Klawitter, J. AU - Seres, T. AU - Szekanecz, Zoltán TI - EFFECTS OF TOFACITINIB THERAPY ON ARGININE AND METHIONINE METABOLITES IN ASSOCIATION WITH VASCULAR PATHOPHYSIOLOGY IN RHEUMATOID ARTHRITIS: A METABOLOMIC APPROACH JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 80 PY - 2021 SP - 421 EP - 422 PG - 2 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-eular.1697 UR - https://m2.mtmt.hu/api/publication/32500463 ID - 32500463 N1 - 334209 LA - English DB - MTMT ER - TY - JOUR AU - Juhász, Balázs AU - Gulyás, Katalin AU - Horváth, Á. AU - Végh, E. AU - Karancsiné Pusztai, Anita AU - Szentpetery, A. AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Hamar, Attila AU - Bodoki, Levente AU - Bhattoa Harjit, Pál AU - Szekanecz, Éva AU - Hodosi, K. AU - Domjan, A. AU - Szamosi, Szilvia AU - Horváth, C. AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Raterman, H. AU - Lems, W. AU - Fitzgerald, O. AU - Szekanecz, Zoltán TI - Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 80 PY - 2021 IS - Suppl 1 SP - 226 EP - 227 PG - 2 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-eular.1951 UR - https://m2.mtmt.hu/api/publication/32499606 ID - 32499606 LA - English DB - MTMT ER - TY - JOUR AU - Karancsiné Pusztai, Anita AU - Hamar, Attila AU - Czókolyová, Monika AU - Gulyás, Katalin AU - Horváth, Ágnes AU - Vegh, Edit AU - Pethő, Zsófia AU - Szamosi, Szilvia AU - Balogh, Emese AU - Bodnár, Nóra AU - Bodoki, Levente AU - Szentpetery, Agnes AU - Bhattoa Harjit, Pál AU - Kerekes, György AU - Juhász, Balázs AU - Szekanecz, Éva AU - Hodosi, Katalin AU - Domjan, Andrea AU - Szántó, Sándor Zoltán AU - Raterman, Hennie G. AU - Lems, Willem F. AU - Szekanecz, Zoltán AU - Szűcs, Gabriella TI - Associations of vascular and bone status in arthritis patients JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 11 PY - 2021 IS - 1 PG - 10 SN - 2045-2322 DO - 10.1038/s41598-021-99071-9 UR - https://m2.mtmt.hu/api/publication/32440947 ID - 32440947 N1 - 322164 AB - Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease. LA - English DB - MTMT ER - TY - JOUR AU - Juhász, Balázs AU - Gulyás, Katalin AU - Horvath, Agnes AU - Vegh, Edit AU - Karancsiné Pusztai, Anita AU - Szentpetery, Agnes AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Hamar, Attila AU - Bodoki, Levente AU - Bhattoa Harjit, Pál AU - Szekanecz, Éva AU - Hodosi, Katalin AU - Domjan, Andrea AU - Szamosi, Szilvia AU - Horváth, Csaba AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Raterman, Hennie G. AU - Lems, Willem F. AU - FitzGerald, Oliver AU - Szekanecz, Zoltán TI - Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients JF - BMC MUSCULOSKELETAL DISORDERS J2 - BMC MUSCULOSKEL DIS VL - 22 PY - 2021 IS - 1 PG - 9 SN - 1471-2474 DO - 10.1186/s12891-021-04708-5 UR - https://m2.mtmt.hu/api/publication/32274642 ID - 32274642 N1 - Department of Oncology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei str. 98, Debrecen, 4032, Hungary Department of Rheumatology, Uppsala University Hospital, Uppsala, Sweden Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary First Department of Medicine, Semmelweis University, Budapest, Hungary Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Department of Rheumatology, Northwest Clinics, Alkmaar, Netherlands Amsterdam Rheumatology and Immunology Centre, Amsterdam, Netherlands Cited By :3 Export Date: 25 May 2022 Correspondence Address: Szekanecz, Z.; Division of Rheumatology, Nagyerdei str. 98, Hungary; email: szekanecz.zoltan@med.unideb.hu Chemicals/CAS: 25 hydroxyvitamin D, 64719-49-9; C reactive protein, 9007-41-4; cathepsin K, 94716-09-3; certolizumab pegol, 428863-50-7; collagen, 9007-34-5; etanercept, 185243-69-0, 200013-86-1, 2055118-96-0; methotrexate, 15475-56-6, 59-05-2, 7413-34-5, 7532-09-4, 6745-93-3, 51865-79-3, 60388-53-6; methylprednisolone, 6923-42-8, 83-43-2; osteocalcin, 136461-80-8; osteoclast differentiation factor, 200145-93-3; parathyroid hormone, 12584-96-2, 68893-82-3, 9002-64-6; Tumor Necrosis Factor Inhibitors AB - Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect. LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Szekanecz, Zoltán AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, E. AU - Pethő, Zoltán Dénes AU - Bodnár, Nóra AU - Gulyás, Katalin AU - Horváth, Á. AU - Soós, B. AU - Bodoki, Levente AU - Bhattoa Harjit, Pál AU - Nagy, Gábor AU - Tajti, Gábor AU - Panyi, György AU - Szekanecz, Éva AU - Domján, A. AU - Hodosi, K. AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Szamosi, Szilvia TI - Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis JF - OSTEOPOROSIS INTERNATIONAL J2 - OSTEOPOROSIS INT VL - 32 PY - 2021 IS - 8 SP - 1621 EP - 1629 PG - 9 SN - 0937-941X DO - 10.1007/s00198-021-05871-0 UR - https://m2.mtmt.hu/api/publication/31878487 ID - 31878487 N1 - 302246 LA - English DB - MTMT ER - TY - JOUR AU - Karancsiné Pusztai, Anita AU - Hamar, Attila AU - Horváth, Ágnes AU - Gulyás, Katalin AU - Végh, Edit AU - Bodnár, Nóra AU - Kerekes, György AU - Czókolyová, Monika AU - Bodoki, Levente AU - Hodosi, Katalin AU - Domján, Andrea AU - Nagy, Gábor AU - Szöllősi, Ibolya AU - Lopez, Luis R. AU - Matsuura, Eiji AU - Prohászka, Zoltán AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Nagy, Zoltán AU - Shoenfeld, Yehuda AU - Szekanecz, Zoltán AU - Szamosi, Szilvia TI - Soluble vascular biomarkers in rheumatoid arthritis and ankylosing spondylitis: effects of one-year anti-TNF-α therapy JF - JOURNAL OF RHEUMATOLOGY J2 - J RHEUMATOL VL - 48 PY - 2021 IS - 6 SP - 821 EP - 828 PG - 8 SN - 0315-162X DO - 10.3899/jrheum.200916 UR - https://m2.mtmt.hu/api/publication/31789607 ID - 31789607 AB - Objective. Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular disease. The treatment of arthritis by tumor necrosis factor-α (TNF-α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized low-density lipoprotein (oxLDL)/β2 glycoprotein I (β2-GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR), and B-type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment. Methods. Fifty-three patients with RA/AS were treated with etanercept or certolizumab pegol for 1 year. Circulating oxLDL/β2-GPI complex (AtherOx), anti-Hsp60 IgG, and BNP8-29 fragment levels were assessed by ELISA. suPAR levels were determined by suPARnostic Quick Triage test. Flow-mediated vasodilation (FMD), carotid intima-media thickness (CIMT), and arterial pulse wave velocity (PWV) were determined by ultrasound. Results. One-year anti-TNF treatment significantly decreased oxLDL/β2-GPI levels, as well as suPAR levels in patients with critically high suPAR levels at baseline. In RA, BNP levels were higher in seropositive vs seronegative patients. Serum levels of these vascular biomarkers variably correlated with lipids, anticitrullinated protein antibodies, rheumatoid factor, and C-reactive protein. CIMT positively correlated with BNP, and PWV with suPAR and anti-Hsp60, whereas FMD inversely associated with anti-Hsp60. In repeated measures ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β2-GPI. CIMT supported the effects of therapy on changes in anti-Hsp60 and suPAR. Conclusion. These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affects the serum levels of oxLDL/β2-GPI, suPAR, and BNP. LA - English DB - MTMT ER - TY - JOUR AU - Karancsiné Pusztai, Anita AU - Hamar, Attila AU - Horvath, Agnes AU - Gulyás, Katalin AU - Végh, Edit AU - Bodnár, Nóra AU - Kerekes, György AU - Czókolyová, Monika AU - Szamosi, Szilvia AU - Bodoki, Levente AU - Hodosi, Katalin AU - Presznerné Domján, Andrea AU - Nagy, Gabor AU - Lopez, Luis AU - Matsuura, Ejii AU - Prohászka, Zoltán AU - Szántó, Sándor Zoltán AU - Nagy, Zoltan AU - Shoenfeld, Yehuda AU - Szekanecz, Zoltán AU - Szűcs, Gabriella TI - Soluble Vascular Biomarkers in Rheumatoid Arthritis and Ankylosing Spondylitis: Effects of One-year Anti-TNF-alpha Therapy JF - ARTHRITIS & RHEUMATOLOGY J2 - ARTHRITIS RHEUMATOL VL - 72 PY - 2020 IS - Suppl. 10 PG - 1 SN - 2326-5191 UR - https://m2.mtmt.hu/api/publication/32120577 ID - 32120577 LA - English DB - MTMT ER -