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Article ; Online: Complexity of the Immune Response Elicited by Different COVID-19 Vaccines, in the Light of Natural Autoantibodies and Immunomodulatory Therapies

Katalin Böröcz / Ágnes Kinyó / Diana Simon / Szabina Erdő-Bonyár / Péter Németh / Timea Berki

International Journal of Molecular Sciences, Vol 24, Iss 6439, p

2023 Volume 6439

Abstract: Despite the abundance of data on the COVID-19 vaccine-induced immune activation, the impact of natural autoantibodies (nAAbs) on these processes is less well defined. Therefore, we investigated potential connections between vaccine efficacy and nAAb ... ...

Abstract	Despite the abundance of data on the COVID-19 vaccine-induced immune activation, the impact of natural autoantibodies (nAAbs) on these processes is less well defined. Therefore, we investigated potential connections between vaccine efficacy and nAAb levels. We were also interested in the impact of immunomodulatory therapies on vaccine efficacy. Clinical residual samples were used for the assessment of the COVID-19 vaccine-elicited immune response (IR) (n=255), as well as for the investigation of the immunization-associated expansion of the nAAb pool (n=185). In order to study the potential interaction between immunomodulatory therapies and the vaccine-induced IR, untreated, healthy individuals and patients receiving anti-TNFα or anti-IL-17 therapies were compared (n total =45). In-house ELISAs (anticitrate synthase, anti-HSP60 and-70) and commercial ELISAs (anti-SARS-CoV-2 ELISAs IgG, IgA, NeutraLISA and IFN-γ release assay ‘IGRA’) were applied. We found significant differences in the IR given to different vaccines. Moreover, nAAb levels showed plasticity in response to anti-COVID-19 immunization. We conclude that our findings may support the theorem about the non-specific beneficial ‘side effects’ of vaccination, including the broadening of the nAAb repertoire. Considering immunomodulation, we suggest that anti-TNFα and anti-IL17 treatments may interfere negatively with MALT-associated IR, manifested as decreased IgA titers; however, the modest sample numbers of the herein presented model might be a limiting factor of reaching a more comprehensive conclusion.
Keywords	COVID-19 ; vaccine ; natural autoantibodies ; ELISA ; immunomodulation ; humoral ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis

Gergely Orsi / Zsofia Hayden / Tamas Cseh / Timea Berki / Zsolt Illes

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain ... ...

Abstract	Abstract Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain volumes and white matter (WM) lesion load in MS. Concentrations of OPN in blood and CSF were related to MRI findings 10.1 ± 2.0 years later in 46 patients with MS. OPN concentration was measured by ELISA, while regional brain volumes and lesion load was assessed by magnetic resonance imaging (MRI) using 3D MPRAGE sequence and automated MR volumetry. OPN measured in the CSF was associated with several regional brain volumes and WM lesion load measured 10.1 ± 2.0 years later. CSF OPN concentration correlated with long-term enlargement of lateral- and inferior lateral ventricles and the elevation of gross CSF volume, in conjunction with the reduction of several cortical/subcortical gray matter and WM volumes. Serum OPN showed no long-term association with regional brain volumes. OPN measured from the CSF but not from the serum was associated with lower regional brain volumes measured a decade later, indicating the primary role of inflammation within the CNS in developing long-term brain related alterations.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Measles Vaccination and Outbreaks in Croatia from 2001 to 2019; A Comparative Study to Other European Countries

Ines Drenjančević / Senka Samardžić / Ana Stupin / Katalin Borocz / Peter Nemeth / Timea Berki

International Journal of Environmental Research and Public Health, Vol 19, Iss 4140, p

2022 Volume 4140

Abstract: Due to the current burden of COVID-19 on public health institutions, increased migration and seasonal touristic traveling, there is an increased risk of epidemic outbreaks of measles, mumps and rubella (MMR). The aim of the present study was to analyze ... ...

Abstract	Due to the current burden of COVID-19 on public health institutions, increased migration and seasonal touristic traveling, there is an increased risk of epidemic outbreaks of measles, mumps and rubella (MMR). The aim of the present study was to analyze the epidemiological data on MMR immunization coverage and the number of measles cases in 2001–2019 in Croatia and a number of European countries. Results revealed a decreasing trend in vaccination in 2001–2019 throughout Europe. However, Croatia and Hungary still have the highest primary and revaccination coverage, compared to other analyzed countries. The highest number of measles cases was in 2017 in Romania. There was no significant correlation between the percentage of primary vaccination and the number of measles cases (r = −0.0528, p = 0.672), but there was a significant negative correlation between the percentage of revaccination and the number of measles cases (r = −0.445, p < 0.0001). In conclusion, the results of the present study emphasize the necessity to perform a full protocol of vaccination to reach appropriate protection from potential epidemic outbreaks. Furthermore, in the light of present migrations, documenting the migrants’ flow and facilitating vaccination as needed is of utmost importance to prevent future epidemics.
Keywords	measles-rubella-mumps vaccination ; Europe ; Croatia ; Medicine ; R
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dynamic Features of Herd Immunity

Katalin Böröcz / Senka Samardžić / Ines Drenjančević / Ákos Markovics / Tímea Berki / Péter Németh

Journal of Clinical Medicine, Vol 11, Iss 1145, p

Similarities in Age-Specific Anti-Measles Seroprevalence Data between Two Countries of Different Epidemiological History

2022 Volume 1145

Abstract: 1) Background: Measles immunization gap(s) raise the concern of potential outbreaks. Both Croatia and Hungary are situated in the vicinity of measles-endemic countries. Potentially compromised immunization activities due to the COVID-19 surge is a ... ...

Abstract	(1) Background: Measles immunization gap(s) raise the concern of potential outbreaks. Both Croatia and Hungary are situated in the vicinity of measles-endemic countries. Potentially compromised immunization activities due to the COVID-19 surge is a ground for concern. Our aim was to compare age-stratified seroprevalence results in the cross-border region. (2) Methods: Anti-MMR specific antibody levels (IgG) of 950 anonymous Croatian samples were compared with previous Hungarian results ( n > 3500 samples), and former Croatian seroprevalence data ( n = 1205). Seropositivity ratios were determined using our self-developed anti-MMR indirect ELISA (Euroimmun IgG ELISA kits were used as control). (3) Results: Measured seropositivity ratios of the Croatian samples were largely overlapping with our earlier published Hungarian data (the lowest seropositivity ratios were measured among individuals of 34–43 years of age with 78% of seropositivity) and are in accordance with earlier published data of Croatian researchers. (4) Conclusion: Although the epidemiological histories of the two countries are different, analogies in age-specific measles susceptibility have been discovered. We suggest that besides the potential coincidence in vaccination ineffectiveness, the inherent biological dynamics of vaccination-based humoral protection might have also contributed to the experienced similarities. Our findings may also serve as a lesson regarding the current anti-COVID-19 vaccination strategy.
Keywords	measles ; MMR ; seropositivity ; susceptibility ; Croatia ; Hungary ; Medicine ; R
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Dora Spantler / Tihamer Molnar / Diana Simon / Timea Berki / Andras Buki / Attila Schwarcz / Peter Csecsei

International Journal of Molecular Sciences, Vol 23, Iss 8789, p

2022 Volume 8789

Abstract: The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum ... ...

Abstract	The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum biomarker studies may help to understand the pathophysiological processes underlying DCI. Samples were collected from patients with aSAH at two time points: (1) 24 h (Day 1) and (2) 5–7 days after ictus. Serum concentrations of eotaxin, FGF-2, FLT-3L, CX3CL1, Il-1b, IL-4, IP-10, MCP3, and MIP-1b were determined using a customized MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel A multiplex assay. The functional outcome was defined by the modified Rankin scale (favorable: 0–2, unfavorable: 3–6) measured on the 30th day after aSAH. One-hundred and twelve patients with aSAH were included in this study. The median level of CX3CL1 and MCP-3 measured on Days 5–7 were significantly higher in patients with DCI compared with those without DCI (CX3CL1: with DCI: 110.5 pg/mL, IQR: 82–201 vs. without DCI: 82.6, 58–119, p = 0.036; and MCP-3: with DCI: 22 pg/mL (0–32) vs. without DCI: 0 (0–11), p < 0.001). IP-10, MCP-3, and MIP-1b also showed significant associations with the functional outcome after aSAH. MCP-3 and CX3CL1 may play a role in the pathophysiology of DCI.
Keywords	aneurysmal subarachnoid hemorrhage ; delayed cerebral ischemia ; functional outcome ; MCP-3 ; CX3CL1 ; IP-10 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model

Szonja Gál / Erzsébet Gajdócsi / Esam Khanfar / Katalin Olasz / Diána Simon / Péter Balogh / Tímea Berki / Péter Németh / Ferenc Boldizsár

International Journal of Molecular Sciences, Vol 24, Iss 9809, p

2023 Volume 9809

Abstract: The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological ... ...

Abstract	The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological autoantibodies (pathAAb). The exact relation between the natAAbs and pathAAbs is still not completely understood; therefore, in the present study, we set out to measure nat- and pathAAb levels against three conserved antigens in a spontaneous autoimmune disease model: the NZB mouse strain which develops autoimmune hemolytic anemia (AIHA) from six months of age. There was an age dependent increase in the natAAb levels in the serum against Hsp60, Hsp70, and the mitochondrial citrate synthase until 6–9 months of age, followed by a gradual decrease. The pathological autoantibodies appeared after six months of age, which corresponded with the appearance of the autoimmune disease. The changes in nat/pathAAb levels were coupled with decreasing B1- and increasing plasma cell and memory B cell percentages. Based on this, we propose that there is a switch from natAAbs towards pathAAbs in aged NZB mice.
Keywords	natural autoantibody ; pathological autoantibody ; autoimmune disease ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	630
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Imported Infections Versus Herd Immunity Gaps; A Didactic Demonstration of Compartment Models Through the Example of a Minor Measles Outbreak in Hungary

Katalin Böröcz / Ákos Markovics / Zsuzsanna Csizmadia / Joseph Najbauer / Timea Berki / Peter Németh

Southeastern European Medical Journal, Vol 5, Iss 1, Pp 1-

2021 Volume 16

Abstract: Introduction: In Hungary, where MMR vaccine coverage is 99%, in 2017, a minor measles epidemic started from imported cases due to two major factors – latent susceptible cohorts among the domestic population and the vicinity of measles-endemic countries. ... ...

Abstract	Introduction: In Hungary, where MMR vaccine coverage is 99%, in 2017, a minor measles epidemic started from imported cases due to two major factors – latent susceptible cohorts among the domestic population and the vicinity of measles-endemic countries. Suspended immunization activities due to the COVID-19 surge are an ominous precursor to a measles resurgence. This epidemiological demonstration is aimed at promoting a better public understanding of epidemiological data. Materials and Methods: Our previous MMR sero-epidemiological measurements (N of total measles cases = 3919, N of mumps cases = 2132, and N of rubella cases = 2132) were analyzed using open-source epidemiological data (ANTSZ) of a small-scale measles epidemic outbreak (2017, Hungary). A simplified SEIR model was applied in the analysis. Results: In case of measles, due to a cluster-specific inadequacy of IgG levels, the cumulative seropositivity ratios (measles = 89.97%) failed to reach the herd immunity threshold (HIT Measles = 92–95%). Despite the fact that 90% of overall vaccination coverage is just slightly below the HIT, unprotected individuals may pose an elevated epidemiological risk. According to the SEIR model, ≥74% of susceptible individuals are expected to get infected. Estimations based on the input data of a local epidemic may suggest an even lower effective coverage rate (80%) in certain clusters of the population. Conclusion: Serological survey-based, historical and model-computed results are in agreement. A practical demonstration of epidemiological events of the past and present may promote a higher awareness of infectious diseases. Because of the high R0 value of measles, continuous large-scale monitoring of humoral immunity levels is important.
Keywords	mmr ; vaccine ; humoral antibody ; epidemics ; seir model ; Medicine ; R
Subject code	612
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Faculty of Medicine Osijek
Document type	Article ; Online
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Article ; Online: Presence of TRPA1 Modifies CD4+/CD8+ T Lymphocyte Ratio and Activation

Katalin Szabó / Ágnes Kemény / Noémi Balázs / Esam Khanfar / Zoltán Sándor / Ferenc Boldizsár / Rolland Gyulai / József Najbauer / Erika Pintér / Tímea Berki

Pharmaceuticals, Vol 15, Iss 57, p

2022 Volume 57

Abstract: Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout—KO) generated by targeted deletion ... ...

Abstract	Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout—KO) generated by targeted deletion of the pore-loop domain of the ion channel. We compared TRPA1 mRNA and protein expression in monocyte and lymphocyte subpopulations isolated from primary and secondary lymphatic organs of wild type (WT) and KO mice. qRT-PCR and flow cytometric studies indicated a higher level of TRPA1 in monocytes than in lymphocytes, but both were orders of magnitude lower than in sensory neurons. We found lower CD4+/CD8+ thymocyte ratios, diminished CD4/CD8 rates, and B cell numbers in the KO mice. Early activation marker CD69 was lower in CD4+ T cells of KO, while the level of CD8+/CD25+ cells was higher. In vitro TcR-mediated activation did not result in significant differences in CD69 level between WT and KO splenocytes, but lower cytokine (IL-1β, IL-6, TNF-α, IL-17A, IL-22, and RANTES) secretion was observed in KO splenocytes. Basal intracellular Ca 2+ level and TcR-induced Ca 2+ signal in T lymphocytes did not differ significantly, but interestingly, imiquimod-induced Ca 2+ level in KO thymocytes was higher. Our results support the role of TRPA1 in the regulation of activation, cytokine production, and T and B lymphocytes composition in mice.
Keywords	TRPA1 ; lymphocytes ; monocytes ; CD4+ cells ; CD8+ cells ; B cells ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ligation of TLR Homologue CD180 of B Cells Activates the PI3K/Akt/mTOR Pathway in Systemic Sclerosis and Induces a Pathological Shift in the Expression of BAFF Receptors

Szabina Erdő-Bonyár / Judit Rapp / Dávid Szinger / Tünde Minier / Gábor Kumánovics / László Czirják / Timea Berki / Diána Simon

International Journal of Molecular Sciences, Vol 23, Iss 6777, p

2022 Volume 6777

Abstract: The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these ... ...

Abstract	The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these pathways, which can be influenced by Toll-like receptors (TLRs), as TLRs can alter the expression of BAFF-binding receptors. Our results show that B-cell stimulation via TLR homologue CD180 phosphorylates Akt in diffuse cutaneous SSc (dcSSc) to a lower extent than in healthy controls (HCs). We found basal downregulated BAFF receptor (BAFF-R) and enhanced transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression in dcSSc B cells, which might enhance the formation of autoantibody-secreting plasma cells. Moreover, this pathological shift was observed in naive B cells, emphasizing the importance of their increase in SSc. Additionally, we measured higher serum levels of autoantibodies to BAFF in dcSSc patients, suggesting that an imbalance in the complex system of BAFF/anti-BAFF autoantibodies/BAFF-binding receptors may contribute to the development of SSc. Anti-CD180 antibody treatment had opposite effects on the expression of BAFF-R and TACI in HC B cells, resulting in similar levels as observed in SSc B cells without stimulation, which argues against the usefulness of such therapy in SSc.
Keywords	CD180 ; TLR ; B cells ; PI3K/Akt ; mTOR ; BAFF-R ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cardiovascular risk factors in coeliac disease (ARCTIC)

Péter Hegyi / Zsolt Szakács / Nelli Farkas / Tímea Berki / Judit Bajor / Tamas Habon / Marcell Imrei / Zsófia Vereczkei / Bálint Kővári / Veronika Papp / Zsuzsanna Lénárt / Balázs Szirmay / Márta Balaskó

BMJ Open, Vol 13, Iss

a protocol of multicentre series of studies

2023 Volume 9

Abstract: Introduction There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD ...

Abstract	Introduction There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD.Methods and analysis This study consists of two case–control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD.Ethics and dissemination The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals.Trial registration number NCT05530070.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
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