TY - JOUR AU - Talib, Mustafa Mohammed Hamid AU - Gyebrovszki, Balázs AU - Fodor, Anna AU - Mészáros, Anna AU - Balog Virág, Kata AU - Barta, Leila Gloria AU - Rojkovich, Bernadette AU - Nagy, György AU - Sármay, Gabriella TI - PD-L1+ Regulatory B Cells from Rheumatoid Arthritis Patients Have Impaired Function in Suppressing IFN-ү and IL-21 Production JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 26 PY - 2025 IS - 7 PG - 16 SN - 1661-6596 DO - 10.3390/ijms26072998 UR - https://m2.mtmt.hu/api/publication/36062346 ID - 36062346 N1 - Department of Immunology, Eötvös Loránd University, Budapest, 1053, Hungary Rheumatology-Rehabilitation Department, Buda Hospital of the Hospitaller Order of Saint John of God, Budapest, 1027, Hungary Department of Rheumatology and Immunology, Semmelweis University, Budapest, 1023, Hungary Heart and Vascular Center, Semmelweis University, Budapest, 1122, Hungary Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, 1089, Hungary Export Date: 24 April 2025; Cited By: 0; Correspondence Address: G. Sármay; Department of Immunology, Eötvös Loránd University, Budapest, 1053, Hungary; email: gabriella.sarmay@ttk.elte.hu AB - Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease. The pathomechanism of RA depends on both B and T cells. Regulatory B cells (Breg) have been shown to suppress T-cell immune responses and play a key role in modulating autoimmune processes. We aimed to investigate the possibility of utilizing PD-L1+ Breg cells in downregulating the Th cells’ immune response in healthy individuals and RA patients. We hypothesized that the PD-1/PD-1L interaction plays a key role in this process, which may be defective in autoimmune diseases. We separated T and B cells from the peripheral blood of healthy volunteers and RA patients by magnetic cell sorting, and Th cells and Treg cells were isolated by fluorescence-activated cell sorting. The cytokine production by CD4+ Th cells was detected by intracellular flow cytometry. CpG and CD40L stimulations were applied to induce PD-L1hi expressing Breg cells. We found that the frequency of PD-L1hi cells is significantly lower in all B-cell subsets in RA compared to healthy controls. Functional analysis of induced PD-L1+ Breg cells in coculture with activated autologous Th cells has shown that healthy control samples containing higher levels of PD-L1hi Breg cells significantly inhibit IFN-ү and IL-21 production by Th cells. In contrast, RA patients’ samples with lower levels of PD-L1hi Breg cells failed to do so. Since the expression of PD-L1 on B cells can be modulated in vitro to induce Breg cell suppressive capacity, these data may provide new perspectives for future therapy for RA. LA - English DB - MTMT ER - TY - JOUR AU - Talib, Mustafa Mohammed Hamid AU - Gyebrovszki, Balázs AU - Bőgér, D. AU - Csomor, R. AU - Mészáros, A. AU - Fodor, A. AU - Rojkovich, B. AU - Sármay, Gabriella TI - Helper T Cells are Hyperactive and Contribute to the Dysregulation of Antibody Production in Patients with Rheumatoid Arthritis JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 18 SN - 1661-6596 DO - 10.3390/ijms251810190 UR - https://m2.mtmt.hu/api/publication/35436264 ID - 35436264 N1 - Department of Immunology, Eötvös Loránd University, Budapest, 1053, Hungary Rheumatology-Rehabilitation Department, Buda Hospital of the Hospitaller Order of Saint John of God, Budapest, 1027, Hungary Export Date: 5 October 2024 Correspondence Address: Sármay, G.; Department of Immunology, Hungary; email: gabriella.sarmay@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Matola, Alexandra Tünde AU - Fülöp, Angéla AU - Rojkovich, Bernadette AU - Nagy, György AU - Sármay, Gabriella AU - Józsi, Mihály AU - Uzonyi, Barbara TI - Autoantibodies against complement factor B in rheumatoid arthritis JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 12 SN - 1664-3224 DO - 10.3389/fimmu.2023.1113015 UR - https://m2.mtmt.hu/api/publication/33692946 ID - 33692946 N1 - Export Date: 20 March 2023 Correspondence Address: Józsi, M.; Department of Immunology, Hungary; email: mihaly.jozsi@ttk.elte.hu AB - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney diseases but not in RA, we set out to further characterize such FB autoantibodies. The isotypes of the analyzed autoantibodies were IgG2, IgG3, IgGκ, IgGλ and their binding site was localized in the Bb part of FB. We detected in vivo formed FB–autoanti-FB complexes by Western blot. The effect of the autoantibodies on the formation, activity and FH-mediated decay of the C3 convertase in solid phase convertase assays was determined. In order to investigate the effect of the autoantibodies on complement functions, hemolysis assays and fluid phase complement activation assays were performed. The autoantibodies partially inhibited the complement-mediated hemolysis of rabbit red blood cells, inhibited the activity of the solid phase C3-convertase and C3 and C5b-9 deposition on complement activating surfaces. In summary, in ACPA-positive RA patients we identified FB autoantibodies. The characterized FB autoantibodies did not enhance complement activation, rather, they had inhibitory effect on complement. These results support the involvement of the complement system in the pathomechanism of RA and raise the possibility that protective autoantibodies may be generated in some patients against the alternative pathway C3 convertase. However, further analyses are needed to assess the exact role of such autoantibodies. LA - English DB - MTMT ER - TY - JOUR AU - Gyebrovszki, Balázs AU - Ács, András AU - Szabó, Dániel AU - Auer, Felícia AU - Novozánszki, Soma AU - Rojkovich, Bernadette AU - Magyar, Anna (Biczókné) AU - Hudecz, Ferenc AU - Vékey, Károly AU - Drahos, László AU - Sármay, Gabriella TI - The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 10 SN - 1661-6596 DO - 10.3390/ijms23105828 UR - https://m2.mtmt.hu/api/publication/32840673 ID - 32840673 N1 - Department of Immunology, Eötvös Loránd University, Budapest, 1117, Hungary MS Proteomics Research Group, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, 1117, Hungary Hevesy György PhD School of Chemistry, Faculty of Science, Eötvös Loránd University, Budapest, 1117, Hungary Translational Glycomics Research Group, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprém, 8200, Hungary Central Laboratory-Microbiology Profile, Molecular Department, National Institute of Hematology and Infectious Diseases, Central Hospital of Southern Pest, Budapest, 1097, Hungary Rheumatology Department III, Polyclinic of the Hospitaller Brothers of St. John of God, Budapest, 1027, Hungary ELKH-ELTE Research Group of Peptide Chemistry, Budapest, 1117, Hungary Export Date: 3 October 2022 Correspondence Address: Sármay, G.; Department of Immunology, Hungary; email: gabriella.sarmay@ttk.elte.hu AB - Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNF alpha production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)(2) fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to Fc gamma R and to trigger TNF alpha release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylation and galactosylation levels of ACPA-IgG negatively correlate with inflammation-related parameters such as CRP, ESR, and RF. Functional assays show that dimerized ACPA-IgG significantly enhances TNF alpha release in an Fc gamma RI-dependent manner, whereas healthy IgG does not. TNF alpha production inversely correlates with the relative intensities of the GO glycoform, which lacks galactose and terminal sialic acid moieties. LA - English DB - MTMT ER - TY - JOUR AU - Matola, Alexandra Tünde AU - Szarka, Eszter AU - Nagy, György AU - Rojkovich, Bernadette AU - Sármay, Gabriella AU - Józsi, Mihály AU - Uzonyi, Barbara TI - AUTOANTIBODIES TO COMPLEMENT COMPONENTS IN RHEUMATOID ARTHRITIS JF - MOLECULAR IMMUNOLOGY J2 - MOL IMMUNOL VL - 150 PY - 2022 SP - 126 EP - 208 PG - 83 SN - 0161-5890 DO - 10.1016/j.molimm.2022.07.003 UR - https://m2.mtmt.hu/api/publication/33111464 ID - 33111464 LA - English DB - MTMT ER - TY - JOUR AU - Matola, Alexandra Tünde AU - Szarka, Eszter AU - Nagy, György AU - Rojkovich, Bernadette AU - Sármay, Gabriella AU - Józsi, Mihály AU - Uzonyi, Barbara TI - KOMPLEMENTKOMPONENSEK ELLENI AUTOANTITESTEK RHEUMATOID ARTHRITISZES BETEGEKBEN JF - IMMUNOLÓGIAI SZEMLE J2 - IMMUNOLÓGIAI SZEMLE VL - 13 PY - 2021 IS - 3 SP - 17 SN - 2061-0203 UR - https://m2.mtmt.hu/api/publication/33111479 ID - 33111479 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Sármay, Gabriella TI - Biologia Futura: Emerging antigen-specific therapies for autoimmune diseases JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 72 PY - 2021 IS - 1 SP - 15 EP - 24 PG - 10 SN - 2676-8615 DO - 10.1007/s42977-021-00074-4 UR - https://m2.mtmt.hu/api/publication/31858377 ID - 31858377 N1 - Funding Agency and Grant Number: Eotvos Lorand University; National Research Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [K 128546] Funding text: Open Access funding provided by Eotvos Lorand University. The funding was provided by the National Research Development and Innovation Office (Grant No. K 128546). LA - English DB - MTMT ER - TY - JOUR AU - Barátki, Balázs Lajos AU - Huber, Krisztina AU - Sármay, Gabriella AU - Matkó, János AU - Kövesdi, Dorottya TI - Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 212 PY - 2019 SP - 14 EP - 21 PG - 8 SN - 0165-2478 DO - 10.1016/j.imlet.2019.06.004 UR - https://m2.mtmt.hu/api/publication/30734809 ID - 30734809 N1 - Funding Agency and Grant Number: Hungarian Scientific Research Fund [OTKA NK 104846]; European Union; European Social Fund [TAMOP 4.2.1/B-09/1/KMR-2010-0003]; MTA Premium Post Doctorate Research Program Funding text: We especially thank Arpad Mikesy for animal husbandry. The project was supported by the Hungarian Scientific Research Fund (OTKA NK 104846), the European Union and the European Social Fund under the grant agreement no. TAMOP 4.2.1./B-09/1/KMR-2010-0003, and by the MTA Premium Post Doctorate Research Program. LA - English DB - MTMT ER - TY - JOUR AU - Barabás, Klaudia AU - Barad, Zsuzsanna AU - Dénes, Ádám AU - Bhattarai, Janardhan P AU - Han, Seong-Kyu AU - Kiss, Endre AU - Sármay, Gabriella AU - Ábrahám, István TI - The Role of Interleukin-10 in Mediating the Effect of Immune Challenge on Mouse Gonadotropin-Releasing Hormone Neurons In Vivo. JF - ENEURO J2 - ENEURO VL - 5 ET - 0 PY - 2018 IS - 5 PG - 13 SN - 2373-2822 DO - 10.1523/ENEURO.0211-18.2018 UR - https://m2.mtmt.hu/api/publication/30316279 ID - 30316279 N1 - Funding Agency and Grant Number: Hungarian Brain Research Program [KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP -2017-00002]; National Science FundationNational Science Foundation (NSF) [112807]; Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs [EFOP-3.6.2-16-2017-00008]; "The role of neuro-inflammation in neurodegeneration: from molecules to clinics" Ministry of Human Capacities [EFOP-3.6.2-16-2017-00008, GINOP-2.3.2-15-2016-00048]; Otago School of Medical Sciences, Department of Physiology, University of Otago Funding text: This work was supported by the Hungarian Brain Research Program (KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP -2017-00002); National Science Fundation (112807); the Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs (EFOP-3.6.1.-16-2016-00004); "The role of neuro-inflammation in neurodegeneration: from molecules to clinics" Ministry of Human Capacities; (EFOP-3.6.2-16-2017-00008), GINOP-2.3.2-15-2016-00048, Stay Alive; and the Otago School of Medical Sciences, Department of Physiology, University of Otago. AB - Immune challenge alters neural functioning via cytokine production. Inflammation has profound impact on the central regulation of fertility, but the mechanisms involved are not clearly defined. The anti-inflammatory cytokine interleukin (IL)-10 is responsible for balancing the immune response in the brain. To examine whether IL-10 has an effect on the function of the gonadotropin-releasing hormone (GnRH) neurons, we first examined the effect of immune responses with distinct cytokine profiles, such as the T cell-dependent (TD) and T cell-independent (TI) B-cell response. We investigated the effect of the TD and TI immune responses on ERK1/2 phosphorylation in GnRH neurons by administering fluorescein isothiocyanate/keyhole limpet hemocyanin (KLH-FITC) or dextran-FITC to female mice. Although dextran-FITC had no effect, KLH-FITC induced ERK1/2 phosphorylation in GnRH neurons after 6 d. KLH-FITC treatment increased the levels of IL-10 in the hypothalamus (HYP), but this treatment did not cause lymphocyte infiltration or an increase in the levels of proinflammatory cytokines. In IL-10 knock-out (KO) mice, KLH-FITC-induced ERK1/2 phosphorylation in the GnRH neurons was absent. We also showed that in IL-10 KO mice, the estrous cycle was disrupted. Perforated patch-clamp recordings from GnRH-GFP neurons, IL-10 immunohistochemistry, and in vitro experiments on acute brain slices revealed that IL-10 can directly alter GnRH neuron firing and induce ERK1/2 phosphorylation. These observations demonstrate that IL-10 plays a role in influencing signaling of GnRH neurons in the TD immune response. These results also provide the first evidence that IL-10 can directly alter the function of GnRH neurons and may help the maintenance of the integrity of the estrous cycle. LA - English DB - MTMT ER - TY - JOUR AU - Szarka, Eszter AU - Aradi, Petra AU - Huber, Krisztina AU - Pozsgay, Judit AU - Végh, Lili AU - Magyar, Anna (Biczókné) AU - Gyulai, Gergő AU - Nagy, György AU - Rojkovich, Bernadette AU - Kiss, Éva AU - Hudecz, Ferenc AU - Sármay, Gabriella TI - Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 19 PY - 2018 IS - 1 PG - 15 SN - 1661-6596 DO - 10.3390/ijms19010326 UR - https://m2.mtmt.hu/api/publication/3323465 ID - 3323465 N1 - Department of Immunology, Eötvös Loránd University, Budapest, 1117, Hungary MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Science, Eötvös Loránd University, Budapest, 1117, Hungary Laboratory of Interfaces and Nanostructures, Institute of Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, 1125, Hungary Rheumatology, Buda Hospital of the Hospitaller Order of St. John of God, Budapest, 1023, Hungary Cited By :11 Export Date: 30 July 2024 Correspondence Address: Sármay, G.; Department of Immunology, Hungary; email: sarmayg@ttk.elte.hu LA - English DB - MTMT ER -