Title CITOTOKSIČNI MEHANIZMI POSREDOVANI GRANULIZINOM I PERFORINOM-2 U PATOGENEZI PSORIJAZE I LIHEN PLANUSA
Title (english) CYTOTOXIC MECHANISMS MEDIATED BY GRANULYSIN AND PERFORIN-2 IN PATHOGENESIS OF PSORIASIS AND LICHEN PLANUS
Author Marijana Vičić
Mentor Larisa Prpić Massari (mentor)
Mentor Vlatka Sotošek Tokmadžić (komentor)
Committee member Gordana Laškarin (predsjednik povjerenstva)
Committee member Branka Marinović (član povjerenstva)
Committee member Hana Mahmutefendić Lučin (član povjerenstva)
Committee member Larisa Prpić Massari (član povjerenstva)
Committee member Vlatka Sotošek Tokmadžić (član povjerenstva)
Granter University of Rijeka Faculty of Medicine (Department of Dermatovenerology) Rijeka
Defense date and country 2020-11-26, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Dermatovenerology
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Thesaurus (MESH - Medical Subject Headings )
Psoriasis
Lichen Planus
Antigens, Differentiation
T-Lymphocytes, Cytotoxic
Perforin
Immunohistochemistry
Abstract Cilj istraživanja: Glavni su ciljevi istraživanja bili utvrditi izražaje citotoksičnih molekula granulizina (GNLY) i perforina-2 (P2) u subpopulacijama limfocita periferne venske krvi te u promijenjenoj i nepromijenjenoj koži bolesnika sa psorijazom i lihenom planusom.
Ispitanici i metode: Izražaje GNLY+ i P2+ stanica u perifernoj krvi istražili smo istovremenim obilježavanjem unutarstaničnih i površinskih biljega u različitim limfocitnim subpopulacijama i monocitima metodom imunofluorescencije, uz očitavanje rezultata protočnim citometrom. Metodom jednostruke imunohistokemije istražili smo izražaje i distribuciju GNLY+ i P2+ stanica, dok smo dvostrukom imunohistokemijom analizirali izražaje i distribuciju CD8+GNLY+ i CD56+GNLY+ stanica u odjeljcima promijenjene i nepromijenjene kože bolesnika sa psorijazom i bolesnika s lihenom planusom u odnosu na zdravu kožu kontrolne skupine.
Rezultati: Učestalost GNLY+ stanica je bila statistički značajno veća u svim stanicama, a P2+ stanica u monocitima (CD14+) periferne krvi obaju skupina bolesnika sa psorijazom te bolesnika s lihenom planusom u odnosu na kontrolnu skupinu, dok se postotak GNLY+, CD3+CD8+GNLY+, CD3+CD56+GNLY+ i CD14+P2+ stanica statistički značajno razlikovao i u perifernoj krvi bolesnika s teškom psorijazom u odnosu na bolesnike s blagom psorijazom. Težina psorijaze je statistički značajno korelirala s udjelima GNLY+, CD3+CD8+GNLY+, CD3+CD56+GNLY+ te CD14+P2+ stanica periferne venske krvi bolesnika sa psorijazom.
Zaključak: Povećana učestalost GNLY+ i P2+ stanica u perifernoj venskoj krvi te u promijenjenoj koži bolesnika sa psorijazom i bolesnika s lihenom planusom te pozitivna korelacija težine psorijaze s udjelom GNLY+ i P2+ stanica upućuju da citotoksični mehanizmi posredovani GNLY i P2 doprinose patogenezi ovih bolesti na sustavnoj i lokalnoj razini. Stoga bi se, u budućnosti, GNLY i P2 mogli koristiti kao biomarkeri za uspješnu procjenu težine i aktivnosti psorijaze.
Abstract (english) Objectives: The main objectives of the study were to determine the expressions of the cytotoxic molecules granulysin (GNLY) and perforin-2 (P2) in the lymphocytes' subpopulations of the peripheral venous blood and in the lesional and nonlesional skin of patients with psoriasis and lichen planus.
Patients and Methods: The expressions of GNLY+ and P2+ cells in the peripheral blood were investigated by simultaneous labelling of intracellular and surface markers in monocytes and in different lymphocytes' subpopulations by immunofluorescence, with a flow cytometer results reading. By single immunohistochemistry, we investigated the expressions and distribution of GNLY+ and P2+ cells, while by double immunohistochemistry we analyzed the expressions and distribution of CD8+GNLY+ and CD56+GNLY+ cells in both sections of lesional and nonlesional skin of patients with psoriasis and lichen planus in relation to the healthy skin of the control group.
Results: The frequency of GNLY+ cells was statistically significantly higher in all cells, and of P2+ cells in monocytes (CD14+) of peripheral blood of both psoriasis patients groups and patients with lichen planus compared to the control group, while the percentage of GNLY+, CD3+CD8+GNLY+, CD3+CD56+GNLY+ and CD14+P2+ cells statistically significantly differed in the peripheral blood of patients with severe and mild psoriasis also. The psoriasis severity statistically significantly correlated with the proportions of GNLY+, CD3+CD8+GNLY+, CD3+CD56+GNLY+ and CD14+P2+ cells in the peripheral venous blood of psoriasis patients.
Conclusion: The increased proportion of GNLY+ and P2+ cells in peripheral venous blood and in lesional and nonlesional skin of patients with psoriasis and lichen planus, as well as a positive correlation of psoriasis severity with the frequency of GNLY+ and P2+ cells suggest that cytotoxic mechanisms mediated by GNLY and P2 contribute to the pathogenesis of these diseases at the systemic and the local level. Therefore, GNLY and P2 could be used in the future as biomarkers for the successful assessment of psoriasis severity and activity
Keywords
Granulizin
Lihen planus
Limfociti T
Stanice NK
Stanice NKT
Stanična imunost
Stanična citotoksičnost
Perforin-2
Vulgarna psorijaza
Keywords (english)
Cytotoxicity
Immunologic
Granuylsin protein
Flow Cytometry
Immunohistochemistry
Lichen Planus
Natural Killer Cells
Perforin
Psoriasis
T-Lymphocytes
Language croatian
URN:NBN urn:nbn:hr:184:046946
Promotion 2021
Study programme Title: Biomedicine Postgraduate (doctoral) study programme Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
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Created on 2021-03-04 18:32:34