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Title:Vloga regulatornih subpopulacij in citokinskih - stat signalnih poti cd4+ t limfocitov pri bolnikih s kronično limfocitno levkemijo
Authors:ID Roškar, Zlatko (Author)
ID Bevc, Sebastjan (Mentor) More about this mentor... New window
ID Goropevšek, Aleš (Comentor)
Files:.pdf DOK_Roskar_Zlatko_2025.pdf (3,88 MB)
MD5: 7CD421055E88264947E40898D07DC0E4
 
Language:Slovenian
Work type:Dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Uvod Kronično limfocitno levkemijo (KLL) označuje kopičenje patoloških B limfocitov, ob tem je spremenjena homeostaza CD4+ T limfocitov, med katerimi imajo največje imunosupresivno delovanje aktivirani T regulatorni limfociti (aTreg). Namen naše raziskave je bil proučiti signalizacijo homeostatskih citokinov, opredeliti spremembe subpopulacij T regulatornih limfocitov med stadiji KLL in v primerjavi z zdravimi preiskovanci ter njihovo povezavo z razširjenostjo bolezni in pogostostjo resnih okužb. Bolniki in metode S pretočno citometrijo smo spremljali aktivacijo signalnih poti (fosforilacijo STAT proteinov) in subpopulacije T regulatornih limfocitov glede na stadij bolezni in oceno tumorske mase (TTM) pri 56 bolnikih s KLL in 20 zdravih preiskovancih. Rezultati Ugotovili smo značilno višje ravni fosforiliacije STAT3 in STAT5 proteinov pri zdravljenih bolnikih s KLL. Delež aTreg je bil značilno povečan pri bolnikih s KLL z napredovalo boleznijo in v značilni pozitivni povezavi s TTM. Za podskupino bolnikov z večjim deležem aTreg ob začetku zdravljenja so bile med spremljanjem značilne pogostejše resne okužbe. Zaključki Večji delež aTreg predstavlja možen označevalec težjega poteka bolezni z infekcijskimi zapleti. Povečana homeostatska signalizacija bi lahko podpirala pomnožitev aTreg, saj so bile zvišane ravni fosforiliracije STAT5 povezane z večjimi deleži aTreg med spremljanjem bolnikov na zdravljenju (in po stimulaciji z antigeni SARS-CoV-2 in vitro).
Keywords:kronična limfocitna levkemija, aktivirani regulatorni T limfociti, signalna pot, imunofenotipizacija
Place of publishing:Maribor
Publisher:[Z. Roškar]
Year of publishing:2025
PID:20.500.12556/DKUM-91617 New window
UDC:616.155.392-006.44-076.3(043.3)
COBISS.SI-ID:241384451 New window
Publication date in DKUM:04.07.2025
Views:188
Downloads:43
Metadata:XML DC-XML DC-RDF
Categories:MF
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:20.01.2025

Secondary language

Language:English
Title:The role of regulatory subpopulations and cytokine-stat signaling pathways of cd4+ t lymphocytes in patients with chronic lymphocytic leukemia
Abstract:Introduction Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of pathological B lymphocytes, with altered homeostasis of CD4+ T lymphocytes, among which activated T regulatory lymphocytes (aTreg) have the highest immunosuppressive activity. The aim of our study was to investigate homeostatic cytokine signalling and to characterize changes in Treg subsets between stages of CLL, in comparison with a healthy population, and in relation to the course of the disease/incidence of serious infections. Patients and Methods Flow cytometry was used to monitor the activation of signalling pathways (phosphorylation of STAT proteins) and Treg subpopulations according to disease stage and total tumour mass (TTM) score in 56 patients with CLL and 20 healthy subjects. Results We found significantly higher phosphorylation levels of STAT3 and STAT5 proteins in treated CLL patients. aTreg proportion was significantly increased in CLL patients with advanced disease and significantly positively correlated with TTM. The subgroup of patients with higher aTreg proportion at treatment initiation was characterised by more frequent serious infections during follow-up. Conclusions A higher proportion of aTreg represents a possible marker of a more severe disease course with infectious complications. Increased homeostatic signalling could support aTreg expansion, as elevated levels of STAT5 phosphorylation were associated with higher aTreg proportions during follow-up of patients on treatment (and after stimulation with SARS-CoV-2 antigens in vitro).
Keywords:chronic lymphocytic leukemia, activated regulatory T lymphocytes, signaling pathway, immunophenotyping


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