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Article: Influence of vascular endothelial growth factor on neutrophil activation in asthmatics.

Gomułka, Krzysztof / Liebhart, Jerzy / Jaskuła, Emilia / Mędrala, Wojciech

2022 Volume 39, Issue 2, Page(s) 275–280

Abstract: Introduction: Asthma is a complex syndrome associated with heterogeneity in the type of inflammation that modulates airway hyperresponsiveness and remodelling. Airway inflammation with neutrophils, cytokines like vascular endothelial growth factor (VEGF) ...

Abstract	Introduction: Asthma is a complex syndrome associated with heterogeneity in the type of inflammation that modulates airway hyperresponsiveness and remodelling. Airway inflammation with neutrophils, cytokines like vascular endothelial growth factor (VEGF) and various gene polymorphisms might be relevant for asthma pathogenesis. Aim: To investigate the expression of CD69 and CD11b markers on peripheral neutrophils after VEGF Material and methods: 122 subjects (82 asthmatics and 40 controls) participated in our study. CD69 and CD11b presence on peripheral blood neutrophils was detected using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP - positive control) and after VEGF stimulation. Genotyping for the VEGF-promoter region was performed by polymerase chain reaction (PCR). Results: Peripheral neutrophil stimulation with VEGF enhances the activity of these cells and induces CD69 and CD11b expression in a dose-dependent manner compared with unstimulated neutrophils ( Conclusions: Our results demonstrate that VEGF might insignificantly activate neutrophils in asthmatics. In addition, the modulated expression of CD69 and CD11b on peripheral neutrophils is not related to potential contribution of the VEGF gene polymorphism.
Language	English
Publishing date	2022-05-09
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2596142-1
ISSN	1642-395X
ISSN	1642-395X
DOI	10.5114/ada.2022.115888
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ability of the immune system to fight viruses highlighted by cytometry and T-cell receptor clonotype assessment: lessons taken before the coronavirus disease 2019 pandemic outbreak.

Jaskuła, Emilia / Lange, Andrzej

Polish archives of internal medicine

2020 Volume 130, Issue 7-8, Page(s) 662–667

Abstract: The intriguing aspects of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to quickly build the rationale behind ... ...

Abstract	The intriguing aspects of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to quickly build the rationale behind the treatment, taking advantage of past analogues. When a new virus strikes, T‑cell receptor γδ cells are in the first line of defense, activated by stress molecules and recognizing some epitopes in a process that is major histocompatibility complex-independent but still specific, eg, cytomegalovirus, as well as participating in the regulatory mechanism-both characteristics are useful in fighting SARS‑CoV‑2. Most deaths occur due to pneumonitis, in the course of which overwhelming inflammation impairs blood oxygenation, calling for artificial ventilation. In fatal cases of coronavirus disease 2019, the balance between the immune response and the inflammatory outcome fails and, therefore, patients at risk, mostly the elderly, show higher levels of anti-SARS‑CoV‑2 antibodies and enhanced inflammation in the lungs. Apparently, there is no feedback control over the antibody production. The investigational use of convalescent plasma, providing antibodies taken from patients who have recovered, was shown to be effective, likely through exerting idiotype‑associated negative control of antibody production. Similarly, the use of mesenchymal stem cells may assist the body regulatory mechanisms, considering the anti‑inflammatory potential of these cells. The use of these 2 immunotherapeutic tools is understandable based on basic immunology and this knowledge may direct the efforts of the medical community aimed at combating the virus.
MeSH term(s)	Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Flow Cytometry ; Humans ; Immune System ; Pandemics ; Pneumonia, Viral/immunology ; Receptors, Antigen, T-Cell/immunology ; SARS-CoV-2
Chemical Substances	Receptors, Antigen, T-Cell
Keywords	covid19
Language	English
Publishing date	2020-05-25
Publishing country	Poland
Document type	Journal Article
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15388
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Article ; Online: Influence of vascular endothelial growth factor on neutrophil activation in asthmatics

Krzysztof Gomułka / Jerzy Liebhart / Emilia Jaskuła / Wojciech Mędrala

Advances in Dermatology and Allergology, Vol 39, Iss 2, Pp 275-

2022 Volume 280

Keywords	asthma ; neutrophils ; vascular endothelial growth factor ; Dermatology ; RL1-803 ; Internal medicine ; RC31-1245
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Termedia Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Peripheral blood eosinophils priming and

Gomułka, Krzysztof / Liebhart, Jerzy / Jaskuła, Emilia / Mędrala, Wojciech

Postepy dermatologii i alergologii

2021 Volume 38, Issue 5, Page(s) 850–854

Abstract: Introduction: Asthma is a complex airway disease with heterogeneity in molecular pathways. Hypersecretion of many cytokines (e.g. vascular endothelial growth factor - VEGF), inflammatory cells infiltration (e.g. eosinophils) and different genetic ... ...

Abstract	Introduction: Asthma is a complex airway disease with heterogeneity in molecular pathways. Hypersecretion of many cytokines (e.g. vascular endothelial growth factor - VEGF), inflammatory cells infiltration (e.g. eosinophils) and different genetic factors (e.g. gene polymorphism) might be responsible for physiological and pathological changes in the course of this chronic disease. Aim: To reveal the possible expression of activation marker CD69 on eosinophils unstimulated and stimulated by VEGF in patients with asthma. Additionally, the influence of a genetic factor (del18 genotype at -2549 -2567 position in the promoter of the VEGF gene) was considered. Material and methods: The study involved 122 participants (82 patients with asthma and 40 healthy controls). CD69 expression on peripheral blood eosinophils was detected by flow cytometry without exogenous stimulation and after Results: CD69 was strongly presented ( Conclusions: Our results may suggest the potential contribution of the VEGF gene polymorphism to the spontaneous increase of eosinophils activity (priming) in patients with asthma. In addition, the results show that VEGF is unlikely to significantly activate eosinophils in asthmatics.
Language	English
Publishing date	2021-11-05
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2596142-1
ISSN	1642-395X
ISSN	1642-395X
DOI	10.5114/ada.2021.103498
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Article ; Online: Cytokine Overproduction and Immune System Dysregulation in alloHSCT and COVID-19 Patients.

Lange, Andrzej / Lange, Janusz / Jaskuła, Emilia

Frontiers in immunology

2021 Volume 12, Page(s) 658896

Abstract: The COVID-19 pathomechanism depends on (i) the pathogenicity of the virus, (ii) ability of the immune system to respond to the cytopathic effect of the virus infection, (iii) co-morbidities. Inflammatory cytokine production constitutes a hallmark of ... ...

Abstract	The COVID-19 pathomechanism depends on (i) the pathogenicity of the virus, (ii) ability of the immune system to respond to the cytopathic effect of the virus infection, (iii) co-morbidities. Inflammatory cytokine production constitutes a hallmark of COVID-19 that is facilitated by inability of adaptive immunity to control virus invasion. The effect of cytokine release syndrome is deleterious, but the severity of it depends on other confounding factors: age and comorbidities. In this study, we analyze the literature data on the post-transplant course of allogeneic hematopoietic stem cell transplanted (alloHSCT) patients, which is affected by generated inflammatory cytokines. The sequence of events boosting cytokine production was analyzed in relation to clinical and laboratory data highlighting the impact of cytokine generation on the post-transplant course. The collected data were compared to those from studies on COVID-19 patients. The similarities are: (i) the damage/pathogen-associated molecular pattern (DAMP/PAMP) stage is similar except for the initiation hit being sterile in alloHSCT (toxic damage of conditioning regimen) and viral in COVID-19; (ii) genetic host-derived factors play a role; (iii) adaptive immunity fails, DAMP signal(s) increases, over-production of cytokines occurs; (iv) monocytes lacking HLADR expression emerge, being suppressor cells hampering adaptive immunity; (v) immune system homeostasis is broken, the patient's status deteriorates to bed dependency, leading to hypo-oxygenation and malnutrition, which in turn stimulates the intracellular alert pathways with vigorous transcription of cytokine genes. All starts with the interaction between DAMPs with appropriate receptors, which leads to the production of pro-inflammatory cytokines, the inflammatory process spreads, tissue is damaged, DAMPs are released and a vicious cycle occurs. Attempts to modify intracellular signaling pathways in patients with post-alloHSCT graft vs host disease have already been undertaken. The similarities documented in this study show that this approach may also be used in COVID-19 patients for tuning signal transduction processes to interrupt the cycle that powers the cytokine overproduction.
MeSH term(s)	Allografts ; COVID-19/immunology ; Cytokine Release Syndrome/immunology ; Cytokines/biosynthesis ; Cytokines/immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; SARS-CoV-2 ; Transplantation Immunology/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2021-06-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.658896
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Peripheral blood eosinophils priming and in vitro VEGF stimulation in asthmatics

Krzysztof Gomułka / Jerzy Liebhart / Emilia Jaskuła / Wojciech Mędrala

Advances in Dermatology and Allergology, Vol 38, Iss 5, Pp 850-

2021 Volume 854

Keywords	asthma ; cd69 ; del/ins ; eosinophils ; vascular endothelial growth factor ; Dermatology ; RL1-803 ; Internal medicine ; RC31-1245
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Termedia Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Immune Response to COVID-19 mRNA Vaccine-A Pilot Study.

Lange, Andrzej / Borowik, Agata / Bocheńska, Jolanta / Rossowska, Joanna / Jaskuła, Emilia

Vaccines

2021 Volume 9, Issue 5

Abstract: Twenty individuals (17 females, 3 males, aged 31-65 years (range), median: 46) who received both doses of the BioNTech Pfizer mRNA vaccine were examined (11 to 31 days, median: 25) after the second dose for the presence of antibodies against peptides of ... ...

Abstract	Twenty individuals (17 females, 3 males, aged 31-65 years (range), median: 46) who received both doses of the BioNTech Pfizer mRNA vaccine were examined (11 to 31 days, median: 25) after the second dose for the presence of antibodies against peptides of SARS-COV-2 and some of MERS-CoV, SARS-CoV1, HCov229E, and HCoVNL63. Clinical evaluation revealed that six people had COVID-19 in the past. We found that: (i) Six people claimed the presence of unwanted effects of vaccination, which were more frequent in those with a history of COVID-19 (4 out of 6 vs. 2 out of 14,
Language	English
Publishing date	2021-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9050488
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Article ; Online: Immune Response to COVID-19 mRNA Vaccine—A Pilot Study

Andrzej Lange / Agata Borowik / Jolanta Bocheńska / Joanna Rossowska / Emilia Jaskuła

Vaccines, Vol 9, Iss 488, p

2021 Volume 488

Abstract: Twenty individuals (17 females, 3 males, aged 31–65 years (range), median: 46) who received both doses of the BioNTech Pfizer mRNA vaccine were examined (11 to 31 days, median: 25) after the second dose for the presence of antibodies against peptides of ... ...

Abstract	Twenty individuals (17 females, 3 males, aged 31–65 years (range), median: 46) who received both doses of the BioNTech Pfizer mRNA vaccine were examined (11 to 31 days, median: 25) after the second dose for the presence of antibodies against peptides of SARS-COV-2 and some of MERS-CoV, SARS-CoV1, HCov229E, and HCoVNL63. Clinical evaluation revealed that six people had COVID-19 in the past. We found that: (i) Six people claimed the presence of unwanted effects of vaccination, which were more frequent in those with a history of COVID-19 (4 out of 6 vs. 2 out of 14, p = 0.037); (ii) All individuals independent of the past history of COVID-19 responded equally well in IgG but those who experienced the disease tended to do better in IgA class (729.04 vs. 529.78 U/mL, p = 0.079); (iii) All those who had experienced the disease had IgG antibodies against nucleocapsid antigens but also 5 out of 14 who had not had the disease (6/6 vs. 5/14, p = 0.014); (iv) Anti S2 antibodies were present in the patients having COVID-19 in the past but also were found in those who had not had the disease (6/6 vs. 8/14, p = 0.144); (v) All vaccinated people were highly positive in the IGRA and the level of released IFN gamma was correlated with the numbers of HLADR positive lymphocytes in the blood ( R = 0.5766, p = 0.008).
Keywords	COVID-19 ; SARS-COV-2 ; mRNA vaccine ; antibodies response ; IFN gamma blood cells release ; Medicine ; R
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Ability of the immune system to fight viruses highlighted by cytometry and T-cell receptor clonotype assessment: lessons taken before the coronavirus disease 2019 pandemic outbreak

Jaskula, Emilia / Lange, Andrzej

Pol Arch Intern Med

Abstract: The intriguing aspects of severe acute respiratory syndrome coronavirus 2 (SARSCoV2) are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to quickly build the rationale behind ... ...

Abstract	The intriguing aspects of severe acute respiratory syndrome coronavirus 2 (SARSCoV2) are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to quickly build the rationale behind the treatment, taking advantage of past analogues. When a new virus strikes, Tcell receptor Î³Î´ cells are in the first line of defense, activated by stress molecules and recognizing some epitopes in a process that is major histocompatibility complex-independent but still specific, eg, cytomegalovirus, as well as participating in the regulatory mechanism-both characteristics are useful in fighting SARSCoV2. Most deaths occur due to pneumonitis, in the course of which overwhelming inflammation impairs blood oxygenation, calling for artificial ventilation. In fatal cases of coronavirus disease 2019, the balance between the immune response and the inflammatory outcome fails and, therefore, patients at risk, mostly the elderly, show higher levels of anti-SARSCoV2 antibodies and enhanced inflammation in the lungs. Apparently, there is no feedback control over the antibody production. The investigational use of convalescent plasma, providing antibodies taken from patients who have recovered, was shown to be effective, likely through exerting idiotypeassociated negative control of antibody production. Similarly, the use of mesenchymal stem cells may assist the body regulatory mechanisms, considering the antiinflammatory potential of these cells. The use of these 2 immunotherapeutic tools is understandable based on basic immunology and this knowledge may direct the efforts of the medical community aimed at combating the virus.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #361315
Database	COVID19

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Article ; Online: CD14 + HLADR - blood values in patients after alloHSCT are highly predictive of survival and infectious complications.

Jaskuła, Emilia / Lange, Janusz / Sędzimirska, Mariola / Suchnicki, Krzysztof / Mordak-Domagała, Monika / Pakos, Helena / Lange, Andrzej

Transplant immunology

2021 Volume 65, Page(s) 101370

Abstract: Background: Cytokine storm described in patients after allogeneic haematopoietic stem cell transplantation (alloHSCT) is associated with the appearance of CD14 + HLADR - in the blood.: Methods: To study the role of CD14 + HLADR - cells 223 patients ... ...

Abstract	Background: Cytokine storm described in patients after allogeneic haematopoietic stem cell transplantation (alloHSCT) is associated with the appearance of CD14 + HLADR - in the blood. Methods: To study the role of CD14 + HLADR - cells 223 patients after alloHSCT followed from 1 month to 15 years. The methods used included flow cytometry for blood cells profiling, nucleic acid tests for viral reactivation, and physician care according to the Polish and international guidelines. Results: We found that CD14 + HLADR - peak values determined during the first 60 post-transplant days were higher in the patients who died than in those who survived in this time interval (mean ± SEM: 3.78 ± 0.67% vs 2.38 ± 0.65%, p < 0.001). Receiver operating characteristic (ROC) analysis showed that CD14 + HLADR - cells level in the blood at cut-off point at 0.71% discriminated the patients as to survival; the patients above the threshold had poorer survival (Kaplan-Meier curve covering 15-year observation) than those below (0.19 vs 0.46, p < 0.001). Infections prevailed other causes of death in the high blood CD14 + HLADR - group (0.61 vs 0.38, p = 0.057). ROC analysis defined the CD4+ blood level at 17.70% as not significantly associated with survival. Multivariate analysis revealed that CD14 + HLADR - cells (HR = 3.47, p < 0.001) and the presence of acute graft-versus-host disease (aGvHD) grade ≥ 3 (HR = 3.82, p = 0.005) adversely impacted the survival. Conclusions: CD14 + HLADR - cells can serve as a biomarker for the risk of fatal complications frequently associated with infections.
MeSH term(s)	Graft vs Host Disease/diagnosis ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies
Language	English
Publishing date	2021-01-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1160846-8
ISSN	1878-5492 ; 0966-3274
ISSN (online)	1878-5492
ISSN	0966-3274
DOI	10.1016/j.trim.2021.101370
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