doktorska disertacija
Zlatko Roškar (Author), Sebastjan Bevc (Mentor), Aleš Goropevšek (Co-mentor)

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;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UM - University of Maribor
Publisher: [Z. Roškar]
UDC: 616.155.392-006.44-076.3(043.3)
COBISS: 241384451 Link will open in a new window
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Other data

Secondary language: English
Secondary title: The role of regulatory subpopulations and cytokine-stat signaling pathways of cd4+ t lymphocytes in patients with chronic lymphocytic leukemia
Secondary 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).
Secondary keywords: chronic lymphocytic leukemia;activated regulatory T lymphocytes;signaling pathway;immunophenotyping;
Type (COBISS): Dissertation
Thesis comment: Univ. v Mariboru, Medicinska fak.
Pages: 101 str.
ID: 25735954