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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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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: Small molecules fail to induce direct reprogramming of adult rat olfactory ensheathing glia to mature neurons.

Portela-Lomba, María / Simón, Diana / Fernández de Sevilla, David / Moreno-Flores, Mª Teresa / Sierra, Javier

Frontiers in molecular neuroscience

2023 Volume 16, Page(s) 1110356

Abstract: An approach to generate new neurons after central nervous system injury or disease is direct reprogramming of the individual's own somatic cells into differentiated neurons. This can be achieved either by transduction of viral vectors that express ... ...

Abstract	An approach to generate new neurons after central nervous system injury or disease is direct reprogramming of the individual's own somatic cells into differentiated neurons. This can be achieved either by transduction of viral vectors that express neurogenic transcription factors and/or through induction with small molecules, avoiding introducing foreign genetic material in target cells. In this work, we propose olfactory ensheathing glia (OEG) as a candidate for direct reprogramming to neurons with small molecules due to its well-characterized neuro-regenerative capacity. After screening different combinations of small molecules in different culture conditions, only partial reprogramming was achieved: induced cells expressed neuronal markers but lacked the ability of firing action potentials. Our work demonstrates that direct conversion of adult olfactory ensheathing glia to mature, functional neurons cannot be induced only with pharmacological tools.
Language	English
Publishing date	2023-02-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2023.1110356
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Article ; Online: Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model.

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

International journal of molecular sciences

2023 Volume 24, Issue 12

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.
MeSH term(s)	Mice ; Animals ; Autoantibodies ; Anemia, Hemolytic, Autoimmune ; Autoimmune Diseases
Chemical Substances	Autoantibodies
Language	English
Publishing date	2023-06-06
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/ijms24129809
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Article ; Online: Dichotomous colorectal cancer behaviour.

Aljama, Sara / Lago, Estela P / Zafra, Olga / Sierra, Javier / Simón, Diana / Santos, Cruz / Pascual, Jesus Rodriguez / Garcia-Romero, Noemi

Critical reviews in oncology/hematology

2023 Volume 189, Page(s) 104067

Abstract: Colorectal cancer (CRC) is the third most common malignant tumor and one of the deadliest cancers. At molecular level, CRC is a heterogeneous disease that could be divided in four Consensus Molecular Subtypes. Given the differences in the disease due to ... ...

Abstract	Colorectal cancer (CRC) is the third most common malignant tumor and one of the deadliest cancers. At molecular level, CRC is a heterogeneous disease that could be divided in four Consensus Molecular Subtypes. Given the differences in the disease due to its anatomical location (proximal and distal colon), another classification should be considered. Here, we review the current knowledge on CRC dichotomic´s behaviour based on two different entities; right and left-sided tumors, their impact on clinical trial data, microbiota spatial composition and the interaction with the nervous system. We discuss recent advances in understanding how the spatial tumor heterogeneity influences the tumor growth, progression, and responses to current therapies.
MeSH term(s)	Humans ; Colorectal Neoplasms/therapy ; Colorectal Neoplasms/drug therapy ; Colonic Neoplasms/pathology
Language	English
Publishing date	2023-07-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.104067
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Article: Investigation of peripheral inflammatory biomarkers in association with suicide risk in major depressive disorder.

Pethő, Borbála / Kovács, Márton Áron / Simon, Diána / Tóth, Tünde / Hajnal, András Sándor / Csulak, Tímea / Hebling, Dóra / Albert, Noémi / Varga, Eszter / Herold, Márton / Osváth, Péter / Vörös, Viktor / Tényi, Tamás / Herold, Róbert

Frontiers in psychiatry

2024 Volume 15, Page(s) 1321354

Abstract: Suicide is the most severe complication of major depressive disorder (MDD). Novel research assumes the role of immunological dysregulation in the background - several studies have reported alterations in the number of inflammatory cells related to both ... ...

Abstract	Suicide is the most severe complication of major depressive disorder (MDD). Novel research assumes the role of immunological dysregulation in the background - several studies have reported alterations in the number of inflammatory cells related to both MDD and suicidality. There are currently no objective, routinely measured parameters to indicate suicidal vulnerability. However, altered inflammatory cell numbers and ratios have been proposed as potential biomarkers of suicide risk (SR). The present research aims to examine changes of these values related to increased SR in MDD as an assumed inflammatory state. We investigated laboratory parameters of psychiatric in-patients diagnosed with MDD (
Language	English
Publishing date	2024-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2024.1321354
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Article ; Online: Altered Levels of Natural Autoantibodies against Heat Shock Proteins in Pregnant Women with Hashimoto's Thyroiditis.

Simon, Diána / Erdő-Bonyár, Szabina / Böröcz, Katalin / Balázs, Noémi / Badawy, Ahmed / Bajnok, Anna / Nörenberg, Jasper / Serény-Litvai, Tímea / Várnagy, Ákos / Kovács, Kálmán / Hantosi, Eszter / Mezősi, Emese / Németh, Péter / Berki, Tímea

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's ... ...

Abstract	The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.
MeSH term(s)	Pregnancy ; Humans ; Female ; Autoantibodies ; Pregnant Women ; Heat-Shock Proteins ; Hashimoto Disease ; Autoimmune Diseases ; HSP70 Heat-Shock Proteins ; Immunoglobulin G ; Chaperonin 60 ; Immunoglobulin M
Chemical Substances	Autoantibodies ; Heat-Shock Proteins ; HSP70 Heat-Shock Proteins ; Immunoglobulin G ; Chaperonin 60 ; Immunoglobulin M
Language	English
Publishing date	2024-01-24
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/ijms25031423
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Article ; Online: Natural Autoantibodies in Biologic-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients: Associations with Vascular Pathophysiology.

Simon, Diána / Kacsándi, Dorottya / Pusztai, Anita / Soós, Boglárka / Végh, Edit / Kerekes, György / Bodoki, Monika / Szamosi, Szilvia / Szűcs, Gabriella / Prohászka, Zoltán / Németh, Péter / Berki, Tímea / Szekanecz, Zoltán

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. ... ...

Abstract	Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (
MeSH term(s)	Humans ; Spondylitis, Ankylosing/drug therapy ; Carotid Intima-Media Thickness ; Autoantibodies ; Tumor Necrosis Factor Inhibitors ; Follow-Up Studies ; Arthritis, Rheumatoid ; Atherosclerosis/complications ; Inflammation/complications ; Biological Products ; Immunoglobulin G ; Immunoglobulin M
Chemical Substances	Autoantibodies ; Tumor Necrosis Factor Inhibitors ; Biological Products ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2024-03-18
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/ijms25063429
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Article ; Online: Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential.

Nörenberg, Jasper / Vida, Péter / Bösmeier, Isabell / Forró, Barbara / Nörenberg, Anna / Buda, Ágnes / Simon, Diana / Erdő-Bonyár, Szabina / Jáksó, Pál / Kovács, Kálmán / Mikó, Éva / Berki, Tímea / Mezősi, Emese / Barakonyi, Alíz

Frontiers in immunology

2024 Volume 15, Page(s) 1382424

Abstract: During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This ... ...

Abstract	During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.
MeSH term(s)	Pregnancy ; Humans ; Female ; Placenta ; Decidua ; HLA-G Antigens/genetics ; HLA-G Antigens/metabolism ; Trophoblasts/metabolism ; Cytokines/metabolism ; Antineoplastic Agents
Chemical Substances	HLA-G Antigens ; Cytokines ; Antineoplastic Agents
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1382424
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Article ; Online: Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.

Molnar, Tihamer / Lehoczki, Andrea / Fekete, Monika / Varnai, Reka / Zavori, Laszlo / Erdo-Bonyar, Szabina / Simon, Diana / Berki, Tímea / Csecsei, Peter / Ezer, Erzsebet

GeroScience

2024

Abstract: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of ... ...

Abstract	The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.
Language	English
Publishing date	2024-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-024-01165-5
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