Određivanje genotipskih i fenotipskih biomarkera kožne barijere u bolesnika s atopijskim dermatitisom

doctoral thesis

• Title (english): Determination of genotypic and fenotypic biomarkers of skin barrier in skin of patients with atopic dermatitis
• Author: Ružica Jurakić Tončić
• Mentor: Branka Marinović (mentor)
• Mentor: Sanja Kežić (komentor); VIAF: 305471531
• Committee member: Liborija Lugović Mihić (predsjednik povjerenstva); VIAF: 305540496
• Committee member: Asija Stipić-Marković (član povjerenstva)
• Committee member: Marija Buljan (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-10-19, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Dermatovenerology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

U ovoj studiji određivani su genotipski i fenotipski biomarkeri kožne barijere kod
bolesnika s atopijskim dermatitisom (AD). U studiju je uključeno 100 odraslih
bolesnika i 50 zdravih ispitanika u razdoblju od siječnja 2016. do srpnja 2017.
godine u Klinici za dermatovenerologiju KBC Zagreb. Za određivanje mutacije
filagrinskog gena korišten je bukalni bris. Uzorkovanjem SC-a uzet je materijal za
određivanje NMF-a, citokina i lipida. Funkcija barijere je mjerena određivanjem
NMF-a, TEWL-a, pH i SA. Nađena je niska učestalost filagrinskih mutacija (4%)
i normalne razine filagrinskih degradacijskih produkata čime zaključujemo da
nedostatak filagrina ne igra značajnu ulogu u etiologiji AD-a u hrvatskoj populaciji.
Lipidi pokazuju značajne razlike između bolesnika i zdravih ispitanika i
povezanost s težinom bolesti i funkcijom kožne barijere. Promjene su izraženije
u lezionalnoj koži.
Određivanje imunoloških markera potvrdilo je prisutnost velikog broja citokina
prirođene i stečene imunosti. Najznačajnija razlika između zdrave i kože
bolesnika nađena je za citokine prirođene imunosti IL-18 i CXCL8, ali značajne
razlike nađene su i za Th1, Th2, Th17 i Th22 citokine. Razina citokina povezana
je s težinom bolesti i funkcijom kožne barijere, a za razliku od lipida povezanost
je izraženija u nelezionalnoj koži. Provedena studija pokazuje pogodnost SC u
određivanje širokog spektra biomarkera koji mogu doprinijeti razvoju ciljane
terapije prilagođene bolesniku.

Abstract (english)

We studied genotype and phenotype biomarkers of epidermal barrier in atopic
dermatitis (AD) patients. Study population included 150 individuals, 100 patients
and 50 healthy controls from 2016 to 2017 at University Department of
Dermatovenereology Clinical Hospital Centre Zagreb. Buccal swab was used for
genotypization and the other biomarkers were determinated in stratum corneum
(SC). We found low prevalence of filaggrin mutations (4%) and normal levels of
filaggrin degradation products suggesting that filaggrin does not play major role
in pathogenesis of AD in our cohort. Lipid levels are significantly changed when
compared AD skin and healthy skin, and significant correlation with disease
severity and barrier function was found. More prominent changes were found in
lesional skin suggesting that majority of observed changes are secondary due to
inflammation. We determinated great number of cytokines of innate and adaptive
immune response. The most significant difference between healthy and AD skin
was found for innate imunity cytokines IL-18 and CXCL8, but significant response
was found for also for Th1, Th2, Th17 and Th22. Cytokine levels were associated
with disease severity and barrier function, and opposite to lipids, correlation was
more prominent in non-lesional skin. This study confirmed that SC is suitable for
determination of wide range of biomarkers which can contribute for development
of precise, patient-based therapy.

• Keywords: Filagrin; Dermatitis; Atopijski; Citokini; Epidermis; Fenotip; Genotip; Biomarkeri
• Keywords (english): Filaggrin; Dermatitis; Atopic; Cytokines; Epidermis; Phenotype; Genotype; Biomarkers
• Language: croatian
• URN:NBN: urn:nbn:hr:105:875771
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Catalog URL: https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-09268?func=find-e&request=Odre%C4%91ivanje+genotipskih+i+fenotipskih+biomarkera+ko%C5%BEne+barijere+u+bolesnika+s+atopijskim+dermatitisom&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=46&y=7&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4=
• Type of resource: Text
• Extent: 95 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-23 09:16:07