@article{MTMT:35333314, title = {B-sejt-gátlás új lehetőségei – tapasztalataink klinikánk beteganyagán}, url = {https://m2.mtmt.hu/api/publication/35333314}, author = {Varga, Borisz and Kovács, László}, journal-iso = {MAGYAR REUMATOL}, journal = {MAGYAR REUMATOLÓGIA}, volume = {65}, unique-id = {35333314}, issn = {0139-4495}, year = {2024}, pages = {155-155}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:35084706, title = {Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation.}, url = {https://m2.mtmt.hu/api/publication/35084706}, author = {Bettacchioli, Eléonore and Saraux, Alain and Tison, Alice and Cornec, Divi and Dueymes, Maryvonne and Foulquier, Nathan and Hillion, Sophie and Roguedas-Contios, Anne-Marie and Benyoussef, Anas-Alexis and Alarcon-Riquelme, Marta E and Pers, Jacques-Olivier and Devauchelle-Pensec, Valérie}, doi = {10.1002/art.42789}, journal-iso = {ARTHRITIS RHEUMATOL}, journal = {ARTHRITIS & RHEUMATOLOGY}, volume = {76}, unique-id = {35084706}, issn = {2326-5191}, abstract = {The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status.Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients.In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher β2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations.These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies.}, year = {2024}, eissn = {2326-5205}, pages = {751-762}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34840255, title = {Identification of immune subsets with distinct lectin binding signatures using multi-parameter flow cytometry: correlations with disease activity in systemic lupus erythematosus}, url = {https://m2.mtmt.hu/api/publication/34840255}, author = {Szabó, Enikő and Faragó, Anna and Bodor, Gergely and Gémes, Nikolett and Puskás, László and Kovács, László and Szebeni, Gábor}, doi = {10.3389/fimmu.2024.1380481}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {15}, unique-id = {34840255}, issn = {1664-3224}, year = {2024}, eissn = {1664-3224}, orcid-numbers = {Kovács, László/0000-0003-4457-1430; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34802087, title = {Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis}, url = {https://m2.mtmt.hu/api/publication/34802087}, author = {Parodis, I. and Lindblom, J. and Toro-Domínguez, D. and Beretta, L. and Borghi, M.O. and Castillo, J. and Carnero-Montoro, E. and Enman, Y. and Mohan, C. and Alarcón-Riquelme, M.E. and Barturen, G. and Nikolopoulos, D.}, doi = {10.1016/j.ekir.2024.03.014}, journal-iso = {KIDNEY INT REP}, journal = {KIDNEY INTERNATIONAL REPORTS}, volume = {9}, unique-id = {34802087}, issn = {2468-0249}, abstract = {Introduction: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options. Methods: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN (n = 41) and active nonrenal lupus (n = 62) versus healthy controls (HCs) (n = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery (n = 26) and a replication (n = 15) set of active LN cases. Results: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis. Unsupervised coexpression network analysis revealed 20 dysregulated gene modules and stratified the active LN population into 3 distinct subgroups. These subgroups were characterized by low, intermediate, and high interferon (IFN) signatures, with differential dysregulation of the “B cell” and “plasma cells/Ig” modules. Drugs annotated to the IFN network included CC-motif chemokine receptor 1 (CCR1) inhibitors, programmed death-ligand 1 (PD-L1) inhibitors, and irinotecan; whereas the anti-CD38 daratumumab and proteasome inhibitor bortezomib showed potential for counteracting the “plasma cells/Ig” signature. In silico analysis demonstrated the low-IFN subgroup to benefit from calcineurin inhibition and the intermediate-IFN subgroup from B-cell targeted therapies. High-IFN patients exhibited greater anticipated response to anifrolumab whereas daratumumab appeared beneficial to the intermediate-IFN and high-IFN subgroups. Conclusion: IFN upregulation and B and plasma cell gene dysregulation patterns revealed 3 subgroups of LN, which may not necessarily represent distinct disease phenotypes but rather phases of the inflammatory processes during a renal flare, providing a conceptual framework for precision medicine in LN. © 2024 International Society of Nephrology}, keywords = {systemic lupus erythematosus; lupus nephritis; Transcriptome; Biologics; Precision Medicine; druggability; trancriptomics}, year = {2024}, eissn = {2468-0249}, pages = {1817-1835}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34656799, title = {Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort}, url = {https://m2.mtmt.hu/api/publication/34656799}, author = {Parodis, Ioannis and Lindblom, Julius and Barturen, Guillermo and Ortega-Castro, Rafaela and Cervera, Ricard and Pers, Jacques-Olivier and Genre, Fernanda and Hiepe, Falk and Gerosa, Maria and Kovács, László and De Langhe, Ellen and Piantoni, Silvia and Stummvoll, Georg and Vasconcelos, Carlos and Vigone, Barbara and Witte, Torsten and Alarcón-Riquelme, Marta E and Beretta, Lorenzo}, doi = {10.1136/ard-2023-224795}, journal-iso = {ANN RHEUM DIS}, journal = {ANNALS OF THE RHEUMATIC DISEASES}, volume = {83}, unique-id = {34656799}, issn = {0003-4967}, abstract = {To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission.We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway.We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.}, keywords = {Autoimmune Diseases; Autoimmunity; Lupus Erythematosus, Systemic; Immune System Diseases; Outcome Assessment, Health Care}, year = {2024}, eissn = {1468-2060}, pages = {889-900}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34193576, title = {EULAR recommendations for the management of systemic lupus erythematosus. 2023 update}, url = {https://m2.mtmt.hu/api/publication/34193576}, author = {Fanouriakis, Antonis and Kostopoulou, Myrto and Andersen, Jeanette and Aringer, Martin and Arnaud, Laurent and Bae, Sang-Cheol and Boletis, John and Bruce, Ian N and Cervera, Ricard and Doria, Andrea and Dörner, Thomas and Furie, Richard A and Gladman, Dafna D and Houssiau, Frederic A and Inês, Luís Sousa and Jayne, David and Kouloumas, Marios and Kovács, László and Mok, Chi Chiu and Morand, Eric F and Moroni, Gabriella and Mosca, Marta and Mucke, Johanna and Mukhtyar, Chetan B and Nagy, György and Navarra, Sandra and Parodis, Ioannis and Pego-Reigosa, José M and Petri, Michelle and Pons-Estel, Bernardo A and Schneider, Matthias and Smolen, Josef S and Svenungsson, Elisabet and Tanaka, Yoshiya and Tektonidou, Maria G and Teng, Yk Onno and Tincani, Angela and Vital, Edward M and van Vollenhoven, Ronald F and Wincup, Chris and Bertsias, George and Boumpas, Dimitrios T}, doi = {10.1136/ard-2023-224762}, journal-iso = {ANN RHEUM DIS}, journal = {ANNALS OF THE RHEUMATIC DISEASES}, volume = {83}, unique-id = {34193576}, issn = {0003-4967}, abstract = {To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.}, keywords = {Autoimmune Diseases; Lupus Erythematosus, Systemic; lupus nephritis}, year = {2024}, eissn = {1468-2060}, pages = {15-29}, orcid-numbers = {Kovács, László/0000-0003-4457-1430; Nagy, György/0000-0003-1198-3228} } @article{MTMT:34477494, title = {Beszámoló a Magyar Reumatológusok Egyesülete és a Magyar Reumatológiai Szakdolgozók Egyesülete idei vándorgyűléséről (Szeged, 2023. szeptember 21-23)}, url = {https://m2.mtmt.hu/api/publication/34477494}, author = {Kovács, László}, journal-iso = {MAGYAR REUMATOL}, journal = {MAGYAR REUMATOLÓGIA}, volume = {64}, unique-id = {34477494}, issn = {0139-4495}, year = {2023}, pages = {223-225}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34191432, title = {A szisztémás lupus erythematosus diagnosztikája}, url = {https://m2.mtmt.hu/api/publication/34191432}, author = {Farkas, Viktória and Kovács, László}, journal-iso = {IMMUNOLÓGIAI SZEMLE}, journal = {IMMUNOLÓGIAI SZEMLE}, volume = {15}, unique-id = {34191432}, issn = {2061-0203}, year = {2023}, pages = {61-71}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34149983, title = {Katasztrófa antifoszfolipid szindróma egy eset kapcsán}, url = {https://m2.mtmt.hu/api/publication/34149983}, author = {Rideg, Adrienn and Dobi, Diána and Kovács, László}, journal-iso = {MAGYAR REUMATOL}, journal = {MAGYAR REUMATOLÓGIA}, volume = {64}, unique-id = {34149983}, issn = {0139-4495}, year = {2023}, pages = {181-182}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} } @article{MTMT:34149961, title = {Differenciáldiagnosztikai kihívás nyelőcső motilitási zavar kapcsán}, url = {https://m2.mtmt.hu/api/publication/34149961}, author = {Ladóczky-Hulló, Daniella and Bocskai, Márta and Kovács, László}, journal-iso = {MAGYAR REUMATOL}, journal = {MAGYAR REUMATOLÓGIA}, volume = {64}, unique-id = {34149961}, issn = {0139-4495}, year = {2023}, pages = {172-173}, orcid-numbers = {Kovács, László/0000-0003-4457-1430} }