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Article ; Online: Associations of the obesity gene FTO variant with complications and comorbidities in patients with type 1 diabetes.

Słomiński, Bartosz / Skrzypkowska, Maria / Myśliwiec, Małgorzata / Trzonkowski, Piotr

2024 Volume 211, Page(s) 111683

Abstract: Background and aims: Because FTO gene is connected with the risk of obesity, cardiovascular disease and hypertension, as well as type 2 diabetes, we hypothesize that the rs9939609 FTO polymorphism may affect type 1 diabetes (T1D) complications and ... ...

Abstract	Background and aims: Because FTO gene is connected with the risk of obesity, cardiovascular disease and hypertension, as well as type 2 diabetes, we hypothesize that the rs9939609 FTO polymorphism may affect type 1 diabetes (T1D) complications and comorbidities. Methods: We have investigated the associations of the FTO gene variant with the T1D and its complications and comorbidities, as well as the serum levels of pro- and anti-inflammatory markers and lipid profiles. Results: The key results of our study are as follows: (1) the rs9939609 FTO polymorphism does not predispose individuals to T1D; (2) AA genotype is associated with an increased risk of overweight and obesity, retinopathy, hypertension, dyslipidemia and celiac disease; (3) AT genotype is associated with a decreased risk of retinopathy and celiac disease, whereas TT genotype is connected with decreased risk of dyslipidemia; (4) the FTO rs9939609 polymorphism affects the inflammatory status as well as lipid profile in T1D patients. Conclusions: Our results, for the first time, comprehensively indicate that the rs9939609 FTO polymorphism could be considered a genetic marker for increased susceptibility to T1D complications and comorbidities as well as suggests importance of FTO-mediated pathways in their etiology.
Language	English
Publishing date	2024-04-24
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2024.111683
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Article ; Online: Comparative Analysis of Fcγ and Complement Receptors Presence on Monocytes in Pulmonary Sarcoidosis and Tuberculosis.

Typiak, Marlena / Trzonkowski, Piotr / Skotarczak, Monika / Dubaniewicz, Anna

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: Sarcoidosis (SA) is a granulomatous disorder, which mostly affects the lungs. Its clinical characteristics resemble tuberculosis (TB), but its treatment is different. The etiology of SA is unknown; however, mycobacterial antigens were proposed as ... ...

Abstract	Sarcoidosis (SA) is a granulomatous disorder, which mostly affects the lungs. Its clinical characteristics resemble tuberculosis (TB), but its treatment is different. The etiology of SA is unknown; however, mycobacterial antigens were proposed as environmental factors in its development. Due to previously revealed immunocomplexemia with mycobacterial antigens in the blood of our SA but not TB patients, and in the search for biomarkers for differential diagnosis of the two disorders, we studied the phagocytic activity of monocytes from both patients' groups with flow cytometry. With the use of this method, we also analyzed the occurrence of receptors for IgG (FcγR) and complement components (CR) at the surface of these monocytes, responsible for phagocytosis of immunocomplexes. We revealed a higher phagocytic activity of monocytes in both disorders, but an increased frequency of monocytes with FcγRIII (CD16) and decreased with CR1 (CD35) receptor in the blood of SA vs. TB patients. With regard to our other genetic study on FcγRIII variants in SA and TB, this may account for the decreased clearance of immunocomplexes and different immune responses in the two diseases. Thus, the presented analysis not only sheds light on the pathomechanisms of SA and TB but may also support their differential diagnosis.
MeSH term(s)	Humans ; Monocytes ; Sarcoidosis, Pulmonary ; Receptors, IgG ; Receptors, Complement ; Tuberculosis ; Sarcoidosis ; Phagocytosis
Chemical Substances	Receptors, IgG ; Receptors, Complement
Language	English
Publishing date	2023-06-03
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/ijms24119713
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Article ; Online: Variation in the Dopamine-4-Receptor Gene in Patients with Type 1 Diabetes.

Słomiński, Bartosz / Skrzypkowska, Maria / Myśliwiec, Małgorzata / Trzonkowski, Piotr

Neuroendocrinology

2023 Volume 113, Issue 8, Page(s) 875–884

Abstract: Introduction: Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the -521C>T DRD4 gene polymorphism may associate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities.: Methods: In ... ...

Abstract	Introduction: Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the -521C>T DRD4 gene polymorphism may associate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. Methods: In this case-control study, we have examined 300 patients with DM1 in comparison to 300 healthy age-matched controls. Utilizing the amplification refractory mutation system-polymerase chain reaction method, we have analyzed the -521C>T polymorphism of dopamine D4 receptor-encoding gene. Obtained results have been evaluated according to diabetes comorbidities, inflammatory markers, CD14++CD16-, and CD14+CD16+ monocyte subsets as well as lipid profile. Results: The key results of our study are as follows: (1) CC genotype and C allele are associated with a reduced risk of DM1 development (OR = 0.593, p = 0.005 and OR = 0.725, p = 0.003, respectively), whereas TT genotype and T allele are associated with a higher risk of DM1 (OR = 1.408, p = 0.04 and OR = 1.380, p = 0.003, respectively); (2) CC genotype is associated with an increased risk of dyslipidemia and retinopathy in diabetic patients (OR = 2.376, p = 0.001 and OR = 2.111, p = 0.01, respectively); (3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16+ monocytes (p = 210-4 and 0.04, respectively); (4) the DRD4 -521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. Conclusion:* Our data imply that the dopaminergic signaling pathways may play an important role in the etiology of DM1 as well as its comorbidities and will provide a new insight into the DM1 risk management. The -521C>T DRD4 gene polymorphism could be considered a genetic marker to predict susceptibility to DM1 as well as retinopathy and dyslipidemia progress in patients with already established disease.
MeSH term(s)	Humans ; Case-Control Studies ; Diabetes Mellitus, Type 1/genetics ; Dopamine ; Genotype ; Lipids ; Receptors, Dopamine/genetics ; Receptors, Dopamine D4/genetics
Chemical Substances	Dopamine (VTD58H1Z2X) ; Lipids ; Receptors, Dopamine ; DRD4 protein, human ; Receptors, Dopamine D4 (137750-34-6)
Language	English
Publishing date	2023-04-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000530765
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Article ; Online: Comparative Analysis of Fcγ and Complement Receptors Presence on Monocytes in Pulmonary Sarcoidosis and Tuberculosis

Marlena Typiak / Piotr Trzonkowski / Monika Skotarczak / Anna Dubaniewicz

International Journal of Molecular Sciences, Vol 24, Iss 9713, p

2023 Volume 9713

Abstract	Sarcoidosis (SA) is a granulomatous disorder, which mostly affects the lungs. Its clinical characteristics resemble tuberculosis (TB), but its treatment is different. The etiology of SA is unknown; however, mycobacterial antigens were proposed as environmental factors in its development. Due to previously revealed immunocomplexemia with mycobacterial antigens in the blood of our SA but not TB patients, and in the search for biomarkers for differential diagnosis of the two disorders, we studied the phagocytic activity of monocytes from both patients’ groups with flow cytometry. With the use of this method, we also analyzed the occurrence of receptors for IgG (FcγR) and complement components (CR) at the surface of these monocytes, responsible for phagocytosis of immunocomplexes. We revealed a higher phagocytic activity of monocytes in both disorders, but an increased frequency of monocytes with FcγRIII (CD16) and decreased with CR1 (CD35) receptor in the blood of SA vs. TB patients. With regard to our other genetic study on FcγRIII variants in SA and TB, this may account for the decreased clearance of immunocomplexes and different immune responses in the two diseases. Thus, the presented analysis not only sheds light on the pathomechanisms of SA and TB but may also support their differential diagnosis.
Keywords	sarcoidosis ; tuberculosis ; monocytes ; Fc gamma receptors ; IgG receptors ; receptors ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Choroid Plexus Volume Change-A Candidate for a New Radiological Marker of MS Progression.

Jankowska, Anna / Chwojnicki, Kamil / Grzywińska, Małgorzata / Trzonkowski, Piotr / Szurowska, Edyta

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 16

Abstract: 1) Background: Multiple sclerosis (MS) is an auto-immune, chronic, neuroinflammatory, demyelinating disease that affects mainly young patients. This progressive inflammatory process causes the chronic loss of brain tissue and results in a deterioration ... ...

Abstract	(1) Background: Multiple sclerosis (MS) is an auto-immune, chronic, neuroinflammatory, demyelinating disease that affects mainly young patients. This progressive inflammatory process causes the chronic loss of brain tissue and results in a deterioration in quality of life. To monitor neuroinflammatory process activity and predict the further development of disease, it is necessary to find a suitable biomarker that could easily be used. In this research, we verify the usability of choroid plexus (CP) volume, a new MS biomarker, in the monitoring of the progression of multiple sclerosis disease. (2) Methods: A single-center, prospective study with three groups of patients was conducted based on the following groups: MS patients who received experimental cellular therapy (Treg), treatment-naïve MS patients and healthy controls. (3) Results: This study concludes that there is a correlation between the CPV/TIV (choroid plexus/total intracranial volume) ratio and the progress of multiple sclerosis disease-patients with MS (MS + Treg) had larger volumes of choroid plexuses. CPV/TIV ratios in MS groups were constantly and significantly growing. In the Treg group, patients with relapses had larger plexuses in comparison to the group with no relapses of MS. A similar correlation was observed for the GD+ group (patients with postcontrast enhancing plaques) compared against the non-GD group (patients without postcontrast enhancing plaques). (4) Conclusion: Choroid plexus volume, due to its immunological function, correlates with the inflammatory process in the central nervous system. We consider it to become a valuable radiological biomarker of MS activity.
Language	English
Publishing date	2023-08-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13162668
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Article ; Online: T regulatory cells metabolism: The influence on functional properties and treatment potential.

Tomaszewicz, Martyna / Ronowska, Anna / Zieliński, Maciej / Jankowska-Kulawy, Agnieszka / Trzonkowski, Piotr

Frontiers in immunology

2023 Volume 14, Page(s) 1122063

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Humans ; T-Lymphocytes, Regulatory ; Immune System ; Autoimmune Diseases ; Autoimmunity
Language	English
Publishing date	2023-03-03
Publishing country	Switzerland
Document type	Journal Article ; Review ; 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.2023.1122063
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Article: Does Massive Bowel Resection in Newborns Affect Further Immunity in Children?

Sznurkowska, Katarzyna / Borkowska, Anna / Zagierska, Agnieszka / Malanowska, Magdalena / Zieliński, Maciej / Zagierski, Maciej / Trzonkowski, Piotr / Łosin, Marcin / Szlagatys-Sidorkiewicz, Agnieszka

Children (Basel, Switzerland)

2024 Volume 11, Issue 1

Abstract: Background: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access ...

Abstract	Background: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. Methods: 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. Results: Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. Conclusions: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.
Language	English
Publishing date	2024-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children11010114
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Article ; Online: Clinical Application of In Vitro Tests for COVID-19 Vaccine Delayed Hypersensitivity Diagnostics.

Romantowski, Jan / Górska, Aleksandra / Zieliński, Maciej / Trzonkowski, Piotr / Rucka, Karolina / Niedoszytko, Marek

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for ... ...

Abstract	Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; CD40 Ligand ; COVID-19/diagnosis ; COVID-19/prevention & control ; In Vitro Techniques ; Drug Hypersensitivity/diagnosis ; Hypersensitivity, Delayed ; COVID-19 Testing
Chemical Substances	COVID-19 Vaccines ; CD40 Ligand (147205-72-9)
Language	English
Publishing date	2023-08-27
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/ijms241713296
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Article ; Online: All roads lead to T regulatory cells.

Trzonkowski, Piotr

Transplantation

2011 Volume 91, Issue 2, Page(s) 150–151

MeSH term(s)	Forkhead Transcription Factors/immunology ; Humans ; Immune Tolerance ; Immunosuppression/methods ; Kidney Transplantation/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Chimera/immunology ; Transplantation Immunology
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors
Language	English
Publishing date	2011-01-27
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0b013e3181ffbb24
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Immunosuppressive properties of amino acid and peptide derivatives of mycophenolic acid.

Siebert, Agnieszka / Cholewiński, Grzegorz / Trzonkowski, Piotr / Rachon, Janusz

European journal of medicinal chemistry

2020 Volume 189, Page(s) 112091

Abstract: Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide ... ...

Abstract	Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide moiety of MPA - tuftsin conjugates influenced the observed activity. Antiproliferative potential of the obtained conjugates was investigated in vitro and MPA amides with threonine methyl ester and conjugate of MPA with retro-tuftisin occurred to be more selective against PBMC in comparison to parent MPA. Both amino acid and peptide derivatives of MPA acted as inosine-5'-monophosphate dehydrogenaze (IMPDH) inhibitors.
MeSH term(s)	Amino Acids/chemistry ; Cell Proliferation ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; IMP Dehydrogenase/antagonists & inhibitors ; Immunosuppressive Agents/chemistry ; Immunosuppressive Agents/pharmacology ; Jurkat Cells ; Leukocytes, Mononuclear/drug effects ; Molecular Structure ; Mycophenolic Acid/chemistry ; Peptide Fragments/chemistry ; Structure-Activity Relationship
Chemical Substances	Amino Acids ; Enzyme Inhibitors ; Immunosuppressive Agents ; Peptide Fragments ; IMP Dehydrogenase (EC 1.1.1.205) ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2020-01-24
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2020.112091
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