TY - JOUR AU - Dézsi, László AU - Mészáros, Tamás AU - Kozma, Gergely Tibor AU - H-Velkei, Mária AU - Oláh, Csaba Zsolt AU - Szabó, Miklós AU - Patkó, Zsófia Panna AU - Fülöp, Tamás AU - Hennies, Mark AU - Szebeni, Miklós AU - Barta, Bálint András AU - Merkely, Béla Péter AU - Radovits, Tamás AU - Szebeni, János TI - A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 44 PY - 2022 IS - 2 SP - 597 EP - 618 PG - 22 SN - 2509-2715 DO - 10.1007/s11357-021-00495-y UR - https://m2.mtmt.hu/api/publication/32666145 ID - 32666145 N1 - Tamás Radovits and János Szebeni contributed equally to the article. AB - A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans. LA - English DB - MTMT ER - TY - JOUR AU - Kozma, Gergely Tibor AU - Mészáros, Tamás AU - Bakos, Tamás AU - Hennies, Mark AU - Bencze, Dániel AU - Uzonyi, Barbara AU - Győrffy, Balázs AU - Cedrone, Edward AU - Dobrovolskaia, Marina A. AU - Józsi, Mihály AU - Szebeni, János TI - Mini-Factor H Modulates Complement-Dependent IL-6 and IL-10 Release in an Immune Cell Culture (PBMC) Model: Potential Benefits Against Cytokine Storm JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 12 PY - 2021 PG - 13 SN - 1664-3224 DO - 10.3389/fimmu.2021.642860 UR - https://m2.mtmt.hu/api/publication/31997628 ID - 31997628 N1 - Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary SeroScience LCC, Budapest, Hungary TECOdevelopment GmbH, Rheinbach, Germany MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary Second Department of Bioinformatics and Pediatrics, Semmelweis University, Budapest, Hungary Lendület Cancer Biomarker Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary Export Date: 25 April 2025; Cited By: 15; Correspondence Address: J. Szebeni; Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; email: szebeni.janos@med.semmelweis-univ.hu LA - English DB - MTMT ER - TY - JOUR AU - Németh, Ágnes AU - Mózes, Miklós AU - Calvier, Laurent AU - Hansmann, Georg AU - Kökény, Gábor TI - The PPAR gamma agonist pioglitazone prevents TGF-beta induced renal fibrosis by repressing EGR-1 and STAT3 JF - BMC NEPHROLOGY J2 - BMC NEPHROL VL - 20 PY - 2019 IS - 1 PG - 9 SN - 1471-2369 DO - 10.1186/s12882-019-1431-x UR - https://m2.mtmt.hu/api/publication/30731425 ID - 30731425 AB - BackgroundIt has been proposed that peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists might reduce renal fibrosis, however, several studies had contradictory results. Moreover, the possible interaction of TGF-beta(1), PPAR gamma, and transcription factors in renal fibrosis have not been investigated. We hypothesized that oral pioglitazone treatment would inhibit TGF-beta-driven renal fibrosis and its progression, by modulating profibrotic transcription factors in TGF-beta(1) transgenic mice.MethodsMale C57Bl/6J mice (control, CTL, n=14) and TGF-beta overexpressing transgenic mice (TGF beta, n=14, having elevated plasma TGF-beta(1) level) were divided in two sets at 10weeks of age. Mice in the first set were fed with regular rodent chow (CTL and TGF beta, n=7/group). Mice in the second set were fed with chow containing pioglitazone (at a dose of 20mg/kg/day, CTL+Pio and TGF beta+Pio, n=7/group). After 5weeks of treatment, blood pressure was assessed and urine samples were collected, and the kidneys were analyzed for histology, mRNA and protein expression.ResultsTGF-beta(1) induced glomerulosclerosis and tubulointerstitial damage were significantly reduced by pioglitazone. Pioglitazone inhibited renal mRNA expression of all the profibrotic effectors: type-III collagen, TGF-beta(1), CTGF and TIMP-1, and alike transcription factors cFos/cJun and protein expression of EGR-1, and STAT3 protein phosphorylation.ConclusionsOral administration of PPAR gamma agonist pioglitazone significantly reduces TGF-beta(1)-driven renal fibrosis, via the attenuation of EGR-1, STAT3 and AP-1. This implies that PPAR gamma agonists might be effective in the treatment of chronic kidney disease patients. LA - English DB - MTMT ER -