Biochemistry, Genetics and Molecular Biology, Clinical Biochemistry, Molecular Medicine, Rheumatology
6
Scopus Publications
Scopus Publications
Identification of potential predictive biomarkers during JAK-inhibitor therapies in rheumatoid arthritis János Rózsa, Dóra Csige, Monika Bodoki, Zsófia Hagymási-Szabó, Ferenc Tóth, Szilvia Szamosi, Ágnes Horváth, Nóra Bodnár, Edit Végh, Sándor Szántó, Gabriella Szűcs, Zsófia Pethő, Zsuzsanna Gyetkó, Levente Bodoki, János Kádas, Zoltán Szekanecz, Szilárd Póliska Human Genomics, 2026 Targeted synthetic therapeutics, such as Janus kinase (JAK) inhibitors, have opened up a new platform for the treatment of various diseases, including rheumatoid arthritis (RA). As with all drugs, the efficacy of different medicine may vary from patient to patient, and there may be different side effects if the expected effect is not achieved. In addition to the uncertain success of treatments, they also place a heavy burden on the health care system, making the identification of potential predictive biomarkers for drug optimisation highly valuable. In order to identify potential predictive biomarkers, 28 patients with RA were recruited and blood samples were taken twice–before medical treatment and after 6 months of continuous therapy. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and after RNA isolation, RNA sequencing was performed using high throughput sequencing technology to generate global gene expression data. Validation of target genes was conducted using real-time quantitative PCR methods. After data analyses we examined the gene expression changes between the two sampling time points and responder versus non-responder groups. 225 genes showed significantly different expression between T6 and T0 samples, while 60 and 66 genes showed differential expression between the responder and non-responder patients at T0 and T6 sampling points, respectively. 13 differentially expressed genes were common between two time points and showed the same direction in regulation. Based on our results, several RA-relevant genes were identified, as a result of the JAK-inhibitor treatments in comparison of T6 versus T0 samples. At both time points, the differentially expressed genes between responder and non-responder groups could separate the samples, however, the separation was not clear. The identified 13 common genes could also partially separate the responder and non-responder groups from each other. These sets of genes could be the source of potential biomarkers, which could help predict the responsiveness of patients to JAK inhibitor therapy.
Clinical Relevance and Methodological Comparison of Anti-MDA5 Antibody Detection: A Five-Year Retrospective and Exploratory Pilot Study Sándor Mogyoróssy, Gábor Nagy, Zoltán Griger, Melinda Nagy-Vincze, Monika Bodoki, Dóra Csige, Tünde Tarr, Éva Zöld, György Pfliegler, Boglárka Csilla Brúgós, Hui Lu, Sarah Tansley, Péter Antal-Szalmás, Andrea Domján, Szilvia Szamosi, Gabriella Szűcs, Zoltán Szekanecz, Ágnes Horváth, Levente Bodoki Biomolecules, 2026 Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are critical biomarkers in myositis, associated with distinct clinical features and prognosis. This study aimed to evaluate the proportion of anti-MDA5 positivity and compare the diagnostic performance of local immunoblotting (IB) with gold-standard immunoprecipitation (IP). We performed a retrospective analysis of 3272 physician-requested anti-MDA5 IB determinations over a five-year period (2019–2023). A subsequent exploratory pilot study of ten Hungarian patients with myositis was conducted to compare IB results with radiolabeled protein IP. Confirmatory in-house enzyme-linked immunosorbent assay (ELISA) was used to distinguish between 140 kDa bands (anti-MDA5 vs. anti-NXP2). Indirect immunofluorescence (IIF) on HEp-2 cells was also evaluated. In the retrospective cohort, 3.7% (n = 121) of samples were non-negative. Among 64 borderline patients, only one (1.6%) had a definitive diagnosis of dermatomyositis (DM). Conversely, the proportion of confirmed myositis cases was notably higher among patients with strong positive IB results. In our exploratory cross-sectional pilot study, complete concordance between the two assays was observed for negative and strong positive results. Discrepancies were noted in borderline and weak positivity ranges, where anti-MDA5 was not detected by IP; instead, alternative autoantibodies were identified. The three IP-confirmed MDA5 positive samples were all validated by ELISA. The characteristic IIF cytoplasmic staining was identifiable in 2 out of 10 cases (20%). In our cohort, borderline IB cases were frequently potential false positives, highlighting the need for careful clinical evaluation. Borderline and weak results require clinical correlation or confirmatory testing to avoid misdiagnosis.
Adipokines as Prognostic Biomarkers in Multiple Myeloma: A Case–Control Study Nóra Obajed Al-Ali, Dóra Csige, László Imre Pinczés, Katalin Farkas, István Rebenku, Andrea Domján, György Panyi, Zoltán Szekanecz, Gabriella Szűcs, Árpád Illés, László Váróczy Medicina Lithuania, 2025 Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β2-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM.
Effects of Tofacitinib Therapy on Circulating Tumour-Associated Antigens and Their Relationship with Clinical, Laboratory and Vascular Parameters in Rheumatoid Arthritis Enikő Sebestyén, Dóra Csige, Péter Antal-Szalmás, Ágnes Horváth, Edit Végh, Boglárka Soós, Zsófia Pethő, Nóra Bodnár, Attila Hamar, Levente Bodoki, Dorottya Kacsándi, Róza Földesi, Edit Kalina, Gábor Nagy, György Kerekes, Béla Nagy, Katalin Hodosi, Szilvia Szamosi, Péter Árkosy, Gabriella Szűcs, Zoltán Szekanecz, Éva Szekanecz Biomolecules, 2025 Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired vascular pathophysiology in RA, as well as about the effects of antirheumatic drugs on TAA production. Therefore, we determined the effects of one-year tofacitinib treatment on TAA levels, as well as correlations of TAA levels with various RA-associated and vascular parameters. Patients and methods: Altogether, 26 RA patients received 5 mg bid or 10 mg bid tofacitinib treatment for 12 months. Ultrasound-based functional vascular assessments, such as common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV), were determined at various timepoints. Serum concentrations of TAAs, including carcinoembryonic antigen (CEA), CA15-3, CA19-9, CA125, CA72-4, human epididymis protein 4 (HE4) and tissue polypeptide antigen (TPA), as well as various cytokines (TNF-α, IL-6, IL-8, VEGF) and PECAM-1 were determined by flow cytometry using a bead-based multiplex assay (LEGENDplex). Results: As previously determined and published, one-year tofacitinib treatment effectively suppressed disease activity and inflammation. Serum CA15-3 and HE4 levels significantly decreased both after 6 and 12 months compared to baseline (p < 0.05). CA19-9 levels significantly increased both after 6 and 12 months, while CEA levels transiently increased after 6 months versus baseline (p < 0.05). CA125, CA72-4 and TPA levels did not change over time. In various regression analyses, TAA levels showed variable, significant, positive associations with the 28-joint disease activity score (DAS28), CRP, ESR, RF, IL-6, TNF-α, IL-8 and PECAM-1 (p < 0.05). In addition, TAAs variably correlated with ccIMT and cfPWV (p < 0.05). Moreover, one-year changes in TAA levels variably correlated with DAS28, RF and some cytokines (p < 0.05), as well as with changes in DAS28, HAQ, CRP, ESR, IL-6, VEGF and ccIMT from baseline to 12 months (p < 0.05). Conclusions: JAK inhibition might decrease the levels of some TAAs and increase those of others. TAA levels might be associated with RA-related and vascular biomarkers. These results suggest that TAAs might play a role in inflammatory processes and vascular pathology underlying RA.
Should ACR/EULAR criteria be revised changing the RF and ACPA scores? Guenter Steiner, Lieve Van Hoovels, Dóra Csige, Mariele Gatto, Annamaria Iagnocco, Zoltán Szekanecz Autoimmunity Reviews, 2024 Current classification criteria for rheumatoid arthritis (RA) encompass clinical and immunological items and are capable of correctly identifying the majority of symptomatic RA patients. The presence of positive rheumatoid factor (RF) and/or and anti-cyclic citrullinated protein/peptide antibodies (ACPA) gaining increasing importance according to their serological titer eases the recognition of RA, yet the debate is open on whether this scoring system ought to be optimized by hierarchizing ACPA or the combination of ACPA and RF over single positivity, prioritizing specificity over sensitivity. The risk of misdiagnosis and misclassification are often entangled, yet they are not the same. In fact, while ideal diagnosis requires 100% sensitivity and specificity, classification criteria are conceived to gather a homogeneous patient population, favoring specificity over sensitivity. Nevertheless, as they are frequently summoned to support the diagnostic process in clinical practice, issues arise on how comprehensive those should be and on how frequently they should be updated in light of novel acquisitions regarding measurable RA-related abnormalities. In this viewpoint two different views on the topic are confronted, discussing the performance of available criteria and the potentiality and pitfalls of their refinement according to novel data on ACPA and RF contribution and emergence of newly discovered specificities.
Stretch-Induced Down-Regulation of HCN2 Suppresses Contractile Activity Job Baffin Kola, Botagoz Turarova, Dora Csige, Ádám Sipos, Luca Varga, Bence Gergely, Farah Al Refai, Iván P. Uray, Tibor Docsa, Karen Uray Molecules, 2023 Although hyperpolarization-activated and cyclic nucleotide-gated 2 channels (HCN2) are expressed in multiple cell types in the gut, the role of HCN2 in intestinal motility is poorly understood. HCN2 is down-regulated in intestinal smooth muscle in a rodent model of ileus. Thus, the purpose of this study was to determine the effects of HCN inhibition on intestinal motility. HCN inhibition with ZD7288 or zatebradine significantly suppressed both spontaneous and agonist-induced contractile activity in the small intestine in a dose-dependent and tetrodotoxin-independent manner. HCN inhibition significantly suppressed intestinal tone but not contractile amplitude. The calcium sensitivity of contractile activity was significantly suppressed by HCN inhibition. Inflammatory mediators did not affect the suppression of intestinal contractile activity by HCN inhibition but increased stretch of the intestinal tissue partially attenuated the effects of HCN inhibition on agonist-induced intestinal contractile activity. HCN2 protein and mRNA levels in intestinal smooth muscle tissue were significantly down-regulated by increased mechanical stretch compared to unstretched tissue. Increased cyclical stretch down-regulated HCN2 protein and mRNA levels in primary human intestinal smooth muscle cells and macrophages. Overall, our results suggest that decreased HCN2 expression induced by mechanical signals, such as intestinal wall distension or edema development, may contribute to the development of ileus.