Imunopatološke i imunogenetičke značajke bolesnika s pemphigus vulgaris u Hrvatskoj

doctoral thesis

• Title (english): Immunopathologic and immunogenetic in pemphigus vulgaris patients in Croatia
• Author: Ines Lakoš Jukić
• Mentor: Branka Marinović (mentor)
• Committee member: Zrinka Bukvić Mokos (predsjednik povjerenstva)
• Committee member: Romana Čeović (član povjerenstva)
• Committee member: Aleksandra Basta-Juzbašić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-10-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Dermatovenerology
• Universal decimal classification (UDC): 613 - Hygiene. Personal health and hygiene. Dietetics. Occupational diseases. Addictions. Sexual hygiene

Abstract

Pemphigus vulgaris (PV) je rijetka, organ-specifična autoimuna bulozna dermatoza, klinički obilježena pojavom mjehura na koži i sluznicama, histološki akantolizom, a imunopatološki tkivno-vezanim i cirkulirajućim protutijelima usmjerenim prema površinskim strukturama keratinocita - dezmogelinu 1 i dezmogleinu 3. Etiopatogeneza PV nije još razjašnjena iako je poznato da bolest nastaje složenom interakcijom genetskih i okolišnih čimbenika.
Cilj ovog istraživanja bio je odrediti imunopatološka i imunogenetička obilježja bolesnika s PV u Hrvatskoj. Istraživanje je uključilo 30 bolesnika s PV koji su liječeni od PV u Klinici za dermatovenerologiju Kliničkog bolničkog centra Zagreb i Medicinskog fakulteta Sveučilišta u Zagrebu od početka 2007. do kraja 2010. godine. Dijagnoza PV postavljena je na temelju kliničke slike, histopatološke i imunofluorescentne pretrage te nalaza ELISA testa za kvantitativno određivanje protutijela usmjerenih prema Dsg1 i Dsg3. Svim bolesnicima je uzeta krv za HLA tipizaciju, za što su potpisali informirani pristanak.
Statističkom analizom dobivenih podataka utvrdili smo da postoji značajno veća učestalost alela HLA, sustava, razreda II: HLA-DRB1*04:02, HLA-DRB1*14:54, HLA-DQB1*03:02, HLA-DQB1*05:03, HLA-DQA1*03:01 i HLA-DQA1*01:04 te statistički značajno manja učestalost alela HLA-DQA1*05:01 u odnosu na kontrolnu skupinu. Rezultati su pokazali i statistički značajno veću učestalost haplotipova HLA-DRB1*04:02-DQB1*03:02-DQA1*01:02, HLA-DRB1*04:02-DQB1*03:02-DQA1*01:04, HLA-DRB1*04:02-DQB1*03:01-DQA1*03:01, HLA-DRB1*14:54-DQB1*05:03-DQA1*03:01 i HLA-DRB1*16:01-DQB1*05:02-DQA1*03:01 u skupini bolesnika s PV u odnosu na kontrolnu skupinu. S obzirom na ključnu ulogu alela HLA-DRB1*04:02 u imunopatogenzi PV, uspoređena je koncentracija protutijela prema Dsg1 i Dsg3 u odnosu na prisustvo ili odsutnost navedenog alela. Rezultati su pokazali statistički značajnu razliku u koncentraciji protutijela usmjerenih prema dezmogleinu 3 u bolesnika koji su imali DRB1*04:02 u odnosu na bolesnika bez navedenog alela. S obzirom na izraziti polimorfizam HLA sustava, potrebna su daljnja istraživanja s većim brojem ispitanika. Za sada nije za očekivati da će HLA tipizacija biti dio standardnog dijagnostičkog algortima kod PV, kao što je npr. kod dermatitis herpetiformis Duhring.

Abstract (english)

The aim of this study was to determine immunopathologic and immunogenetic characteristics in group of our patients with PV.
This retrospective study sampled patients (N=30) treated for PV at the Department of Dermatology and Venereology, University Hospital Center Zagreb, from January 2007 to 31 December 2010. The diagnosis of PV was based on clinical, histological and immunofluorescence studies as well on ELISA testing for detection of serum antibodies against Dsg1 and Dsg3. Additionally, serum samples were collected for HLA typing, for which all patients have signed informed consent.
Results of the study revealed significantly higher frequencies of HLA-DRB1*04:02, HLA-DRB1*14:54, HLA-DQB1*03:02, HLA-DQB1*05:03, HLA-DQA1*03:01 and HLA-DQA1*01:04 allele in PV patients compared to healthy blood donors. HLA-DQA1*05:01 allele was significantly underrepresented in group of PV patients. We have also observed positive association between HLA-DRB1*04:02-DQB1*03:02-DQA1*01:02, HLA-DRB1*04:02-DQB1*03:02-DQA1*01:04, HLA-DRB1*04:02-DQB1*03:01-DQA1*03:01, HLA-DRB1*14:54-DQB1*05:03-DQA1*03:01 and HLA-DRB1*16:01-DQB1*05:02-DQA1*03:01 haplotypes and PV. Additionally, regarding the role of HLA-DRB1*04:02 in pathogenesis of PV, we have determined values of autoantibodies against Dsg3 in group of PV patients who carried this allele compared to those without it. Anti-Dsg3 antibody levels were significantly higher in patients carring HLA-DRB1*04:02.
Because polymorphism is hallmark of HLA system, further studies with a larger patient series are needed to clarify the role of genetics in pathophysiological mechanism of PV.

• Keywords: pemphigus vulgaris; imunogenetika; venerologija; dermatologija
• Keywords (english): pemphigus vulgaris; immunogenetics; venereology; dermatology
• Language: croatian
• URN:NBN: urn:nbn:hr:105:838681
• Project: Number: 108-000000-0105; Title: Autoimune bulozne dermatoze u Republici Hrvatskoj; Leader: Branka Marinović; Jurisdiction: Croatia; Funder: Ministarstvo znanosti, obrazovanja i športa
• 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/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-20019?func=find-e&request=Imunopatolo%C5%A1ke+i+imunogeneti%C4%8Dke+zna%C4%8Dajke+bolesnika+s+pemphigus+vulgaris+u+Hrvatskoj&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=0&y=0&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: 54 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-15 11:48:13