Vrijednost biljega hrskavice serumskog hondroitin sulfata epitopa 846 i urinarnog C-terminalnog telopeptida kolagena tipa II u ocjeni težine hemofilične artropatije

doctoral thesis

• Title (english): The value of cartilage biomarkers serum chondroitin sulfate epitope 846 and urinary C-terminal telopeptide of type II collagen in assessing the severity of haemophilic arthropathy
• Author: Nataša Kalebota
• Mentor: Porin Perić (mentor)
• Mentor: Silva Zupančić-Šalek (komentor)
• Committee member: Tomislav Đapić (predsjednik povjerenstva)
• Committee member: Branimir Anić (član povjerenstva)
• Committee member: Simeon Grazio (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Orthopedics); Zagreb
• Defense date and country: 2024-10-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Orthopedics
• Universal decimal classification (UDC): 617 - Surgery. Orthopaedics. Ophthalmology

Abstract

Provedeno je istraživanje vrijednosti biljega uCTX-II i CS846 u ocjeni težine hemofilične artropatije (HA) te njihove povezanosti s koštanim biljezima osteokalcinom, koštanom ALP i CTX-I. Analizirana je uloga ADAMTS-4 u HA te je učinjen proteomski profil plazme. Uključeno je 53 bolesnika s hemofilijom, od kojih 27 s teškom i 26 s blagom te 52 zdrava ispitanika. HA ocijenjena je kliničkim i ultrazvučnim HEAD-US skorom. Korištene su metode ELISA dok je proteomska analiza plazme provedena tekućinskom kromatografijom masene spektrometrije. Rezultati pokazuju da uCTX-II ima najviše vrijednosti u teškoj hemofiliji i pozitivnu korelaciju s kliničkim i UZV skorom u cijeloj skupini bolesnika. CS846 nije pokazao razlike u vrijednostima među skupinama, pokazuje negativnu korelaciju s kliničkim i UZV skorom u blagoj hemofiliji i s ukupnim skorom u cijeloj skupini bolesnika. Koštani biljezi nisu pokazali značajne razlike ili korelacije s kliničkim i UZV skorom, niti s biljezima hrskavice, osim što je uCTX-II pokazao korelacije s koštanom ALP i CTX-I. Analiza ADAMTS-4 nije otkrila značajne razlike između skupina, a korelacije s UZV i kliničkim skorovima uglavnom nisu bile značajne. Proteomska analiza identificirala je proteine potencijalno povezane s patofiziologijom HA. Među njima, analiza koncentracija IGF-1 i CTSG nije otkrila značajne razlike. IGF-1 negativno korelira s UZV skorom u blagoj i teškoj hemofiliji, kao i s kliničkim skorom u teškoj hemofiliji. CTSG ne korelira s kliničkim skorom i uglavnom nije pokazao korelaciju s UZV skorom.
Zaključak: Rezultati ukazuju na potencijal uCTX-II kao biljega za procjenu težine i praćenje hemofilične artropatije, dok IGF-1 pridonosi razumijevanju patofiziologije bolesti.

Abstract (english)

Our aim was to examine the value of uCTX-II and CS846 in assessing the severity of HA, alongside evaluating ADAMTS-4, osteocalcin, bone ALP, and CTX-I. Plasma proteomic analysis was conducted. The study included 53 hemophilia patients (27 severe, 26 mild) and 52 healthy controls. HA severity was assessed using clinical and ultrasonographic HEAD-US scores. uCTX-II levels were highest in severe hemophilia and correlated positively with clinical and US scores across all patients. CS846 showed no significant differences among groups but negatively correlated with clinical and US scores in mild hemophilia and total scores across all patients. Bone markers did not significantly differ or correlate with clinical and US scores, except for uCTX-II, which correlated with bone ALP and CTX-I. ADAMTS-4 analysis revealed no significant group differences, and correlations with US and clinical scores were generally insignificant. Proteomic analysis identified potentially relevant proteins. IGF-1 negatively correlated with US scores in both mild and severe hemophilia, as well as with clinical scores in severe hemophilia, while CTSG showed no correlation with clinical scores and generally did not correlate with US scores. In conclusion, our findings suggest the potential of uCTX-II for assessing HA severity, while IGF-1 contributes to understanding disease pathophysiology.

• Keywords: Hemofilija A; osteokalcin; faktor rasta sličan inzulinu 1; proteomika; kost i kosti
• Keywords (english): Hemophilia A; Osteocalcin; Insulin-like growth factor 1; Proteomics; Bone and Bones
• Language: croatian
• URN:NBN: urn:nbn:hr:105:475323
• 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)
• Type of resource: Text
• Extent: 136 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-11-27 12:14:14