Značenje alarmina HMGB1 i S100A12 te njihova receptora RAGE u juvenilnom idiopatskom artritisu

doctoral thesis

• Title (english): The significance of alarmins HMGB1 and S100A12 and their receptor RAGE in juvenile idiopathic arthritis
• Author: Dubravka Bobek; MBZ: 251135
• Mentor: Marija Jelušić-Dražić (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2014-12-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Razumijevanje imunopatogeneze juvenilnog idiopatskog artritisa (JIA) još uvijek je
nepotpuno. Cilj ovog rada bio je utvrditi značenje proteina visoke pokretljivosti iz
skupine 1 (HMGB1,engl. high mobility group box 1), proteina koji veže kalcij
S100A12 (S100A12, engl. calcium-binding protein S100A12) i njihova topljiva
receptora za krajnje produkte uznapredovale glikozilacije sRAGE (engl. soluble
receptor for advanced glycation end products) u JIA. Uključeno je 102 djece sa JIA i 28
djece kontrolne skupine kojima je izvađena periferna krv prije započetog liječenja.
Serumska razina alarmina analizirana je ELISA testom, dok je izražaj gena određen u
mononuklearima periferne krvi kvantitativnim PCR-om. U sistemskom tipu JIA (sJIA)
utvrđene su značajno više serumske razine HMGB1 u odnosu na oligoartikularni (P <
0,000) i poliartikularni (P < 0,002) tip JIA te kontrolnu skupinu (P < 0,032).
Istovremeno, serumska razina (P < 0,036) kao i genski izražaji (P < 0,007) sRAGE bili
su statistički značajno niži u sJIA u odnosu na kontrolu. K tome, serumski HMGB1 u
sJIA djece bio je statistički značajno povezan s ubrzanom sedimentacijom eritrocita (r =
0,51; P < 0,001), povišenom razinom C-reaktivnog proteina (r=0,52; P < 0,000) i
povišenom razinom α2-globulina (r= 0,50; P < 0,001), dok je sRAGE i pokazao
značajnu, ali negativnu korelaciju sa istim proteinima akutne faze. Navedeno ukazuje
na to da HMGB1, kao medijator prirođene imunosti, u interakciji sa sRAGE sudjeluje u
imunopatogenezi sJIA te može služiti kao biomarker za određivanje aktivnosti i
moguća meta u liječenju sJIA.

Abstract (english)

Our understanding of the imunopathogenesis of juvenile idiopathic arthritis (JIA) is
still incomplete. The aim of this study was to determine the significance of high
mobility group box 1 (HMGB1), calcium-binding protein S100A12 and their
soluble receptor for advanced glycation end products (sRAGE) in JIA. We included
102 children with JIA (28 childen with systemic-onset JIA, 39 children with
oligoarticular-onset JIA, and 35 children with polyarticular-onset JIA) and 28
children as control group and harvested peripheral blood before any therapy was
introduced. The serum levels of the alarmins were determined by ELISA, while
gene expression in mononuclears was assessed by quantitative PCR. The level of
the HMGB1 protein was significantly higher in the group of children with systemic
JIA (sJIA), as compared to the olygoarticular (P < 0,000) or polyarticular (P <
0,002) subtype of JIA and control group (P < 0,032). The children with sJIA had a
significant reduction of sRAGE protein in the serum (P < 0.036) and the gene
expression (P < 0,007) of sRAGE. Additionally, serum HMGB1 in sJIA children
was positively correlated with ESR (r = 0,51; P < 0,001), C-reactive protein
(r=0,52; P < 0,000) levels and α2 globulin (r= 0,50; P < 0,001), while sRAGE
serum level showed significantly close but inverse relationship with the same
proteins of acute phase. These data indicate that HMGB1, a mediator of innate
immunity, through interactions with sRAGE contributes to imunopathogenesis of
sJIA. Furthermore, HMGB1 may serve as a biomarker for determining disease
activity and a potential target of therapy in systemic JIA patients.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:002733
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 170 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 07:27:12