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Article ; Online: Modulatory Role of TPPP3 in Microtubule Organization and Its Impact on Alpha-Synuclein Pathology.

Oláh, Judit / Lehotzky, Attila / Szénási, Tibor / Berki, Tímea / Ovádi, Judit

2022 Volume 11, Issue 19

Abstract: Parkinson's disease is characterized by locomotion deficits, dopaminergic neuronal loss and alpha-synuclein (SYN) aggregates; the Tubulin Polymerization Promoting Protein (TPPP/p25 or TPPP1) is also implicated in these processes. The moonlighting and ... ...

Abstract	Parkinson's disease is characterized by locomotion deficits, dopaminergic neuronal loss and alpha-synuclein (SYN) aggregates; the Tubulin Polymerization Promoting Protein (TPPP/p25 or TPPP1) is also implicated in these processes. The moonlighting and chameleon TPPP1 modulates the dynamics/stability of the multifunctional microtubule network by promoting its acetylation and bundling. Previously, we identified the microtubule-associated TPPP3, a homologue of TPPP1 lacking its N-terminus; however, its involvement in physiological or pathological processes was not elucidated. In this work, we have shown the modulatory role of TPPP3, similarly to TPPP1, in microtubule organization, as well as its homo- and hetero-associations with TPPP1. TPPP3, in contrast to TPPP1, virtually does not bind to SYN; consequently, it does not promote SYN aggregation. Its anti-aggregative potency is achieved by counteracting the formation of the TPPP1-SYN pathological complex/aggregation leading to Parkinsonism. The interactions of TPPP3 have been determined and quantified in vitro with recombinant human proteins, cell extracts and in living human cells using different methods including bifunctional fluorescence complementation. The tight association of TPPP3 with TPPP1, but not with SYN, may ensure a unique mechanism for its inhibitory effect. TPPP3 or its selected fragments may become a leading agent for developing anti-Parkinson agents.
MeSH term(s)	Cell Extracts ; Cytoskeletal Proteins/metabolism ; Humans ; Microtubules/metabolism ; Parkinson Disease/metabolism ; Recombinant Proteins/metabolism ; Tubulin/metabolism ; alpha-Synuclein/metabolism
Chemical Substances	Cell Extracts ; Cytoskeletal Proteins ; Recombinant Proteins ; SNCA protein, human ; TPPP3 protein, human ; Tubulin ; alpha-Synuclein
Language	English
Publishing date	2022-09-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11193025
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Article ; Online: Splenectomy at Early stage of Autoimmune Arthritis Delayed Inflammatory Response and Reduced Joint Deterioration in Mice.

Khanfar, Esam / Olasz, Katalin / Gál, Szonja / Gajdócsi, Erzsébet / Kajtár, Béla / Kiss, Tamás / Balogh, Péter / Berki, Timea / Boldizsár, Ferenc

Clinical and experimental immunology

2024

Abstract: The spleen plays a role in innate- and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human ...

Abstract	The spleen plays a role in innate- and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4 weeks interval with the rhG1 antigen. Mice were splenectomized on day 7 (SPE1) or day 35 (SPE2) after the initiation of immunization, and were tested for clinical severity, joint radiological- and histological changes, serum levels of inflammatory cytokines and autoantibodies, and rhG1-specific immune responses, and compared to those in control mice with spleen left intact. Circulating Tregs and T-helper subset ratios in the spleen and inguinal lymph nodes were also examined using flow cytometry. The onset of severe inflammatory response was significantly delayed in SPE1 and SPE2 groups compared to control mice at early stages of GIA, which was associated with increased circulating Tregs. After the third immunization, as disease progressed, the severity scores were robustly increased in all mice. Nevertheless, in splenectomized mice, we observed reduced joint deterioration and cartilage damage, more Th2 cells in lymph nodes, and reduced levels of pro-inflammatory cytokines and autoantibodies in their sera. Mesenteric lymph node cells of splenectomized mice exhibited weaker response in vitro against the rhG1 antigen compared to control mice spleen. In conclusion, splenectomy in early stages of GIA delayed the inflammatory response, suggesting a protective effect against the development and progression of severe destructive arthritis.
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxae013
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Article ; Online: Professional Athletes Maintain High TNF-Alpha or IFN-Gamma Related Inflammatory Status after Recovering from COVID-19 Infection without Developing a Neutralizing Antibody Response.

Ambrus, Mira / Fodor, Eszter / Berki, Timea / Müller, Veronika / Uhlár, Ádám / Hornyák, István / Lacza, Zsombor

Sports (Basel, Switzerland)

2023 Volume 11, Issue 5

Abstract: Introduction: Professional athletes are endangered by COVID-19 and belong to the high-risk population due to their lifestyle. To obtain information on the behavior of COVID-19 in professional athletes, serological, cytokine, and virus neutralization ... ...

Abstract	Introduction: Professional athletes are endangered by COVID-19 and belong to the high-risk population due to their lifestyle. To obtain information on the behavior of COVID-19 in professional athletes, serological, cytokine, and virus neutralization capacities were analyzed. Materials and methods: Hungarian national teams participated in international sports events during the early phases of the COVID-19 epidemic in 2020. Altogether, 29 professional athletes volunteered to donate plasma. Their serological status was evaluated by IgA, IgM, and IgG ELISAs and the highest virus neutralization titer in an in vitro live tissue assay. Plasma cytokine patterns were analyzed with a Bioplex multiplex ELISA system. Results: Surprisingly, only one athlete (3%) had anti-SARS-CoV-2 IgG, while IgA was more common (31%). Neither plasma showed direct virus neutralization in a titer over 1:10; hence, they were not suitable for reconvalescent treatment. The 'cytokine storm' markers IL-6 and IL-8 were at baseline levels. In contrast, either the TNF-alpha-related cytokines or the IFN-gamma-associated cytokines were elevated. There was a strong negative correlation between the TNF-alpha- or IFN-gamma-related cytokines. Conclusions: Professional athletes are susceptible to the SARS-CoV-2 infection without developing long-term immunity through neutralizing immunoglobulins. Elevated secretory and cellular immunity markers indicate that these systems are probably responsible for virus elimination in this subpopulation.
Language	English
Publishing date	2023-04-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704239-X
ISSN	2075-4663 ; 2075-4663
ISSN (online)	2075-4663
ISSN	2075-4663
DOI	10.3390/sports11050097
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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.

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

International journal of molecular sciences

2023 Volume 24, Issue 7

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.
MeSH term(s)	Humans ; COVID-19 Vaccines ; COVID-19 ; Immunoglobulin G ; Vaccination ; Antibodies, Viral ; Autoantibodies ; Immunomodulation ; Immunity ; Immunoglobulin A
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin G ; Antibodies, Viral ; Autoantibodies ; Immunoglobulin A
Language	English
Publishing date	2023-03-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076439
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Article ; Online: Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis.

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

Scientific reports

2021 Volume 11, Issue 1, Page(s) 23604

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 ...

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.
MeSH term(s)	Adult ; Aged ; Brain/diagnostic imaging ; Brain/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis/blood ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Osteopontin/blood ; Osteopontin/cerebrospinal fluid ; Osteopontin/metabolism ; Young Adult
Chemical Substances	Osteopontin (106441-73-0)
Language	English
Publishing date	2021-12-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-03173-3
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Article: Dynamic Features of Herd Immunity: Similarities in Age-Specific Anti-Measles Seroprevalence Data between Two Countries of Different Epidemiological History.

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

Journal of clinical medicine

2022 Volume 11, Issue 4

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 (
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11041145
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Article ; Online: Splenectomy modulates the immune response but does not prevent joint inflammation in a mouse model of RA.

Khanfar, Esam / Olasz, Katalin / Gajdócsi, Erzsébet / Jia, Xinkai / Berki, Timea / Balogh, Péter / Boldizsár, Ferenc

Clinical and experimental immunology

2022 Volume 209, Issue 2, Page(s) 201–214

Abstract: The spleen is the largest secondary lymphoid organ which is involved in the development of B cells and also in systemic (auto)immune responses. Using the recombinant human G1 domain-induced arthritis (GIA) model in splenectomized and control BALB/c mice, ...

Abstract	The spleen is the largest secondary lymphoid organ which is involved in the development of B cells and also in systemic (auto)immune responses. Using the recombinant human G1 domain-induced arthritis (GIA) model in splenectomized and control BALB/c mice, we investigated the role of the spleen in the induction and pathogenesis of autoimmune arthritis. Splenectomized mice developed GIA with a similar clinical picture to the control group. However, we observed significant alterations in the humoral and cellular immune responses in splenectomized mice. In the sera of the splenectomized mice, we found lower pro-inflammatory cytokine and anti-rhG1 IgM levels, but higher IL-4, anti-rhG1 IgG1 and anti-CCP and RF antibodies. The arthritis induction in the splenectomized group was associated with a significant expansion of activated helper T cells and an increase in the proportion of the circulating B1 and marginal zone B cell subsets. Importantly, immunization of the splenectomized mice with rhG1 induced the formation of germinal centers in the inguinal- and mesenteric lymph nodes (i/mLNs) which showed an active immune response to rhG1. Finally, both B and T cells from the mLNs of the splenectomized mice showed decreased intracellular Ca2+ signaling than those of the control group. Collectively, these findings indicate that the presence of the spleen is not critical for the induction of GIA, and in its absence the autoimmune arthritis is most likely promoted through the compensatory activity of the i/mLNs. However, our data implies the immunological role of the spleen in arthritis which could be further assessed in human RA.
MeSH term(s)	Animals ; Arthritis ; Autoimmune Diseases ; Disease Models, Animal ; Humans ; Immunity ; Immunoglobulin G ; Inflammation ; Mice ; Mice, Inbred BALB C ; Splenectomy
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2022-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxac052
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Article ; Online: Measles Vaccination and Outbreaks in Croatia from 2001 to 2019; A Comparative Study to Other European Countries.

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

International journal of environmental research and public health

2022 Volume 19, Issue 7

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.
MeSH term(s)	COVID-19 ; Croatia/epidemiology ; Disease Outbreaks ; Europe ; Humans ; Measles/epidemiology ; Measles/prevention & control ; Mumps/epidemiology ; Rubella ; Vaccination
Language	English
Publishing date	2022-03-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19074140
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Article ; Online: Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.

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

International journal of molecular sciences

2022 Volume 23, Issue 15

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.
MeSH term(s)	Biomarkers ; Brain Ischemia/complications ; Cerebral Infarction/complications ; Chemokine CXCL10 ; Humans ; Subarachnoid Hemorrhage
Chemical Substances	Biomarkers ; Chemokine CXCL10
Language	English
Publishing date	2022-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23158789
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Article ; Online: An Optimized Flow Cytometric Method to Demonstrate the Differentiation Stage-Dependent Ca

Bajnok, Anna / Serény-Litvai, Timea / Temesfői, Viktória / Nörenberg, Jasper / Herczeg, Róbert / Kaposi, Ambrus / Berki, Timea / Mezosi, Emese

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: ... Calcium ( ... ...

Abstract	Calcium (Ca
MeSH term(s)	Humans ; B-Lymphocytes ; B-Lymphocyte Subsets/metabolism ; Antibody-Producing Cells ; Receptors, Antigen, B-Cell/metabolism ; Cell Differentiation
Chemical Substances	Receptors, Antigen, B-Cell
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24109107
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