@article{MTMT:34831850, title = {Single-Cell Multi-Omics Map of Cell Type–Specific Mechanistic Drivers of Multiple Sclerosis Lesions}, url = {https://m2.mtmt.hu/api/publication/34831850}, author = {Elkjaer, Maria L. and Hartebrodt, Anne and Oubounyt, Mhaned and Weber, Anna and Vitved, Lars and Reynolds, Richard and Thomassen, Mads and Rottger, Richard and Baumbach, Jan and Illés, Zsolt László}, doi = {10.1212/NXI.0000000000200213}, journal-iso = {NEUROL-NEUROIMMUNOL}, journal = {NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION}, volume = {11}, unique-id = {34831850}, issn = {2332-7812}, year = {2024}, eissn = {2332-7812}, orcid-numbers = {Elkjaer, Maria L./0000-0002-8596-142X; Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:34592444, title = {New Enhancing MRI Lesions Associate with IL-17, Neutrophil Degranulation and Integrin Microparticles: Multi-Omics Combined with Frequent MRI in Multiple Sclerosis}, url = {https://m2.mtmt.hu/api/publication/34592444}, author = {Illés, Zsolt László and Jorgensen, Malene Moller and Baek, Rikke and Bente, Lisa-Marie and Lauridsen, Jorgen T. and Hyrlov, Kirsten H. and Aboo, Christopher and Baumbach, Jan and Kacprowski, Tim and Cotton, Francois and Guttmann, Charles R. G. and Stensballe, Allan}, doi = {10.3390/biomedicines11123170}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {11}, unique-id = {34592444}, abstract = {Background: Blood-barrier (BBB) breakdown and active inflammation are hallmarks of relapsing multiple sclerosis (RMS), but the molecular events contributing to the development of new lesions are not well explored. Leaky endothelial junctions are associated with increased production of endothelial-derived extracellular microvesicles (EVs) and result in the entry of circulating immune cells into the brain. MRI with intravenous gadolinium (Gd) can visualize acute blood-barrier disruption as the initial event of the evolution of new lesions. Methods: Here, weekly MRI with Gd was combined with proteomics, multiplex immunoassay, and endothelial stress-optimized EV array to identify early markers related to BBB disruption. Five patients with RMS with no disease-modifying treatment were monitored weekly using high-resolution 3T MRI scanning with intravenous gadolinium (Gd) for 8 weeks. Patients were then divided into three groups (low, medium, or high MRI activity) defined by the number of new, total, and maximally enhancing Gd-enhancing lesions and the number of new FLAIR lesions. Plasma samples taken at each MRI were analyzed for protein biomarkers of inflammation by quantitative proteomics, and cytokines using multiplex immunoassays. EVs were characterized with an optimized endothelial stress EV array based on exosome surface protein markers for the detection of soluble secreted EVs. Results: Proteomics analysis of plasma yielded quantitative information on 208 proteins at each patient time point (n = 40). We observed the highest number of unique dysregulated proteins (DEPs) and the highest functional enrichment in the low vs. high MRI activity comparison. Complement activation and complement/coagulation cascade were also strongly overrepresented in the low vs. high MRI activity comparison. Activation of the alternative complement pathway, pathways of blood coagulation, extracellular matrix organization, and the regulation of TLR and IGF transport were unique for the low vs. high MRI activity comparison as well, with these pathways being overrepresented in the patient with high MRI activity. Principal component analysis indicated the individuality of plasma profiles in patients. IL-17 was upregulated at all time points during 8 weeks in patients with high vs. low MRI activity. Hierarchical clustering of soluble markers in the plasma indicated that all four MRI outcomes clustered together with IL-17, IL-12p70, and IL-1 beta. MRI outcomes also showed clustering with EV markers CD62E/P, MIC A/B, ICAM-1, and CD42A. The combined cluster of these cytokines, EV markers, and MRI outcomes clustered also with IL-12p40 and IL-7. All four MRI outcomes correlated positively with levels of IL-17 (p < 0.001, respectively), and EV-ICAM-1 (p < 0.0003, respectively). IL-1 beta levels positively correlated with the number of new Gd-enhancing lesions (p < 0.01), new FLAIR lesions (p < 0.001), and total number of Gd-enhancing lesions (p < 0.05). IL-6 levels positively correlated with the number of new FLAIR lesions (p < 0.05). Random Forests and linear mixed models identified IL-17, CCL17/TARC, CCL3/MIP-1 alpha, and TNF-alpha as composite biomarkers predicting new lesion evolution. Conclusions: Combination of serial frequent MRI with proteome, neuroinflammation markers, and protein array data of EVs enabled assessment of temporal changes in inflammation and endothelial dysfunction in RMS related to the evolution of new and enhancing lesions.Particularly, the Th17 pathway and IL-1 beta clustered and correlated with new lesions and Gd enhancement, indicating their importance in BBB disruption and initiating acute brain inflammation in MS. In addition to the Th17 pathway, abundant protein changes between MRI activity groups suggested the role of EVs and the coagulation system along with innate immune responses including acute phase proteins, complement components, and neutrophil degranulation.}, keywords = {PLASMA; COMPLEMENT; COAGULATION; Mass spectrometry; MULTIPLE SCLEROSIS; MRI; gadolinium; biomarker; blood brain barrier; IL-17; IL-1 beta; endothelial stress; EV array; enhancing lesion}, year = {2023}, eissn = {2227-9059}, orcid-numbers = {Illés, Zsolt László/0000-0001-9655-0450; Jorgensen, Malene Moller/0000-0003-1381-3863; Lauridsen, Jorgen T./0000-0001-9889-6236; Aboo, Christopher/0000-0001-7295-7459; Stensballe, Allan/0000-0002-9888-1955} } @article{MTMT:34453589, title = {Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis : A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control}, url = {https://m2.mtmt.hu/api/publication/34453589}, author = {Pavlekovics, Márk and Engh, Marie Anne and Lugosi, Katalin and Szabó, László and Hegyi, Péter and Terebessy, Tamás and Csukly, Gábor and Molnár, Zsolt and Illés, Zsolt László and Lovas, Gábor}, doi = {10.3390/biomedicines11123180}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {11}, unique-id = {34453589}, abstract = {Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.}, keywords = {relapse; Meta-analysis; Intravenous immunoglobulin; Myasthenia gravis; Plasma Exchange; [Meta-analysis]}, year = {2023}, eissn = {2227-9059}, orcid-numbers = {Engh, Marie Anne/0000-0003-4269-5130; Hegyi, Péter/0000-0003-0399-7259; Terebessy, Tamás/0000-0002-7494-6064; Csukly, Gábor/0000-0002-5006-9407; Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:34311596, title = {Whole blood miRNAs in relapsing MS patients treated with dimethyl fumarate in the phase 4 TREMEND trial}, url = {https://m2.mtmt.hu/api/publication/34311596}, author = {Elkjaer, Maria L. and Lohse, Rikke M. and Burton, Mark and Mendoza, Jason P. and Thomassen, Mads and Sejbaek, Tobias and Illés, Zsolt László}, doi = {10.1016/j.jneuroim.2023.578145}, journal-iso = {J NEUROIMMUNOL}, journal = {JOURNAL OF NEUROIMMUNOLOGY}, volume = {381}, unique-id = {34311596}, issn = {0165-5728}, abstract = {We investigated the impact of dimethyl fumarate (DMF), an oral therapy for relapsing multiple sclerosis (MS), on blood microRNA (miRNA) signatures and neurofilament light (NFL) levels. DMF normalized miR-660-5p and modulated various miRNAs associated with the NF-kB pathway. These alterations reached a peak 4-7 months after treatment. Notably, particular miRNAs correlated with high or low NFL levels, implying their potential role as markers of treatment efficacy. Our findings broaden the understanding of DMF's immunomodulatory effects and may aid in predicting treatment responses.}, keywords = {MULTIPLE SCLEROSIS; miRNA; NF-kB; Neurofilament light chain (NfL); Dimethyl-fumarate (DMF)}, year = {2023}, eissn = {1872-8421}, orcid-numbers = {Burton, Mark/0000-0002-3782-5933; Sejbaek, Tobias/0000-0002-7682-2188; Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:34198121, title = {Circulating microRNAs correlate with structural and functional MRI parameters in patients with multiple sclerosis}, url = {https://m2.mtmt.hu/api/publication/34198121}, author = {Geiger, Lili and Orsi, Gergely and Cseh, Tamás and Gombos, Katalin and Illés, Zsolt László and Czéh, Boldizsár}, doi = {10.3389/fnmol.2023.1173212}, journal-iso = {FRONT MOL NEUROSCI}, journal = {FRONTIERS IN MOLECULAR NEUROSCIENCE}, volume = {16}, unique-id = {34198121}, issn = {1662-5099}, year = {2023}, eissn = {1662-5099}, orcid-numbers = {Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:34053132, title = {Treatment of relapsing multiple sclerosis in Hungary – consensus recommendation from the Hungarian neuroimmunology society}, url = {https://m2.mtmt.hu/api/publication/34053132}, author = {Rajda, Cecília and Rózsa, Csilla and Mike, Andrea and Lovas, Gábor and Mezei, Zsolt and Jakab, Gábor and Ács, Péter and Rum, Gábor and Simó, Magdolna and Jobbágy, Zita and Bíró, Zita and Trauninger, Anita and Imre, Piroska and Mátyás, Klotild and Deme, István and Illés, Zsolt László and Csépány, Tünde}, doi = {10.1186/s13023-023-02789-0}, journal-iso = {ORPHANET J RARE DIS}, journal = {ORPHANET JOURNAL OF RARE DISEASES}, volume = {18}, unique-id = {34053132}, issn = {1750-1172}, abstract = {Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.}, year = {2023}, eissn = {1750-1172}, orcid-numbers = {Rajda, Cecília/0000-0002-0252-4778; Mezei, Zsolt/0000-0002-3797-2191; Simó, Magdolna/0000-0002-1652-2407; Illés, Zsolt László/0000-0001-9655-0450; Csépány, Tünde/0000-0002-8305-3209} } @article{MTMT:33658156, title = {Hypothesis of a potential BrainBiota and its relation to CNS autoimmune inflammation}, url = {https://m2.mtmt.hu/api/publication/33658156}, author = {Elkjaer, Maria L. and Simon, Lukas and Frisch, Tobias and Bente, Lisa-Marie and Kacprowski, Tim and Thomassen, Mads and Reynolds, Richard and Baumbach, Jan and Roettger, Richard and Illés, Zsolt László}, doi = {10.3389/fimmu.2022.1043579}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33658156}, issn = {1664-3224}, abstract = {Infectious agents have been long considered to play a role in the pathogenesis of neurological diseases as part of the interaction between genetic susceptibility and the environment. The role of bacteria in CNS autoimmunity has also been highlighted by changes in the diversity of gut microbiota in patients with neurological diseases such as Parkinson's disease, Alzheimer disease and multiple sclerosis, emphasizing the role of the gut-brain axis. We discuss the hypothesis of a brain microbiota, the BrainBiota: bacteria living in symbiosis with brain cells. Existence of various bacteria in the human brain is suggested by morphological evidence, presence of bacterial proteins, metabolites, transcripts and mucosal-associated invariant T cells. Based on our data, we discuss the hypothesis that these bacteria are an integral part of brain development and immune tolerance as well as directly linked to the gut microbiome. We further suggest that changes of the BrainBiota during brain diseases may be the consequence or cause of the chronic inflammation similarly to the gut microbiota.}, keywords = {MULTIPLE-SCLEROSIS; DIVERSITY; pathology; Health; Immune; Microbiota; microbiome; microbiome; gut-brain axis; CNS autoimmunity; INVARIANT T-CELLS; brainbiome; brainbiota; bacterial transcripts}, year = {2022}, eissn = {1664-3224}, orcid-numbers = {Baumbach, Jan/0000-0002-0282-0462; Roettger, Richard/0000-0003-4490-5947; Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:33297349, title = {Investigation of oxidative stress in patients with multifocal motor neuropathy}, url = {https://m2.mtmt.hu/api/publication/33297349}, author = {Patzkó, Ágnes and Deli, Gabriella and Cseh, Tamás and Beleznay, Zsuzsa and Nagy, Lajos and Kéki, Sándor and Mike, Andrea and Pál, Endre and Komoly, Sámuel and Illés, Zsolt László and Szántóné Csongor, Alexandra and Pfund, Zoltán}, doi = {10.18071/isz.75.0385}, journal-iso = {IDEGGYOGY SZEMLE}, journal = {IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE}, volume = {75}, unique-id = {33297349}, issn = {0019-1442}, abstract = {Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN. Bevezetés: A multifokális motoros neuropathia (MMN) ritka, immunmediált progresszív betegség, ami kizárólag a motoros idegeket érinti. Habár számos tanulmány leírta az oxidatív stressz szerepét a perifériás neuropathiákban, MMN-ben még nem vizsgálták ennek a patomechamizmusnak a szerepét. Módszerek: Tanulmányunkban prospektíven meg­ha­tá­roztuk 10 beteg L-arginin-, valamint szimmetrikus és aszimmetrikus dimetil-arginin- (SDMA- és ADMA-) szintjét, melyek az L-arginin/NO útvonal résztvevői, és szerepet játszanak mind a krónikus gyulladásban, mind az oxidatív stresszben. Az L-arginin, az ADMA és az SDMA szérum­koncentrációját HPLC-vel mértük az intravénás immunglobulin- (IVIG-) kezelés előtt és után 10 MMN-es és 10 egészséges kontrollbetegben. Minden betegnél végez­tünk elektrofiziológiai mérést és vizsgáltuk az antiganglio­zid antitestek jelenlétét a szérumban. Eredmények: Az MMN-es betegeknél szignifikánsan magasabb az ADMA (p = 0,0048; 0,98 és 0,63) és az SDMA szérumszintje (p = 0,001; 0,88 és 0,51), mint az egészséges kontrolloknál, míg az L-arginin szintjében változást nem találtunk. Az életkorra mint kovariánsra kontrollálva (többszörös lineáris regresszióval) az ADMA- (B = –0,474; p = 0,041) és az SDMA- (B = –0,896; p < 0,0005) szérumszintek az MMN szignifikáns prediktorainak bizonyultak. Az IVIG-terápia szignifikánsan csökkentette az ADMA szérumkoncentrációját (p = 0,025; 0,98 és 0,84) és tendenciát mutatott az SDMA szintjének csökkentésére (p = 0,1; 0,88 és 0,74). Nem találtunk összefüggést a dimetil-aminok szintje és az antigangliozid antitestek jelenléte között. A motoros idegek kondukciós blokkhoz köthető motoros funkciózavara javult közvetlenül az IVIG-kezelést követően. Következtetések: A dimetil-aminok szintje emelkedett az MMN-betegek szérumában, és csökken IVIG-kezelés hatására. Ezek az eredmények támogatják az oxidatív stressz jelenlétét.}, keywords = {oxidatív stressz; immunpatogenezis; multifokális motoros neuropathia; biomarkerek; ADMA; SDMA; IVIG-kezelés}, year = {2022}, eissn = {2498-6208}, pages = {385-393}, orcid-numbers = {Illés, Zsolt László/0000-0001-9655-0450} } @article{MTMT:32716642, title = {A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis}, url = {https://m2.mtmt.hu/api/publication/32716642}, author = {Elkjaer, Maria L. and Röttger, Richard and Baumbach, Jan and Illés, Zsolt László}, doi = {10.3389/fimmu.2022.761225}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {32716642}, issn = {1664-3224}, year = {2022}, eissn = {1664-3224}, orcid-numbers = {Illés, Zsolt László/0000-0001-9655-0450} } @misc{MTMT:32635269, title = {Extracellular circulating miRNAs as potential biomarkers in multiple sclerosis and epilepsy}, url = {https://m2.mtmt.hu/api/publication/32635269}, author = {Geiger, Lili and Horváth, Réka and Janszky, József Vladimír and Kecskés, Miklós and Orsi, Gergely and Tóth, Márton and Miseta, Attila János and Illés, Zsolt László and Gombos, Katalin and Czéh, Boldizsár}, unique-id = {32635269}, year = {2022}, orcid-numbers = {Janszky, József Vladimír/0000-0001-6100-832X; Miseta, Attila János/0000-0002-7984-3347; Illés, Zsolt László/0000-0001-9655-0450} }