Utjecaj polimorfizma HLA gama bloka na pojavu reakcije transplantata protiv primatelja u transplantaciji krvotvornih matičnih stanica od nesrodnog davatelja

master's thesis

• Title (english): The impact of HLA gamma block polymorphism on the occurrence of graft versus host disease in hematopoietic stem cell transplantation from unrelated donor
• Author: Zoe Milošev
• Mentor: Zorana Grubić (mentor)
• Committee member: Zorana Grubić (predsjednik povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Committee member: Mirta Tkalec (član povjerenstva)
• Committee member: Julija Erhardt (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Geni glavnog sustava tkivne podudarnosti (geni HLA) tipiziraju se u rutinskom postupku u
pripremi za alogeničnu transplantaciju krvotvornih matičnih stanica (TKMS). To su geni HLA-A,
-B, -C, -DRB1 i -DQB1. Nepodudarnost u genima HLA glavni je rizični faktor za razvoj neželjenih
ishoda nakon TKMS. Unatoč podudaranju u klasičnim genima HLA, moguće je nepodudaranje u
drugim genima unutar regije HLA. U ovom istraživanju tipizirali smo skupinu od 33 para bolesniknesrodni davatelj (podudarnost HLA 9/10) za polimorfizam unutar gena C4 u regiji HLA gama
bloka, smještenog u središnjoj regiji HLA te ispitali povezanost s pojavom reakcije presatka protiv
primatelja (GvHD). Određivanje polimorfizama unutar HLA gama bloka napravljeno je pomoću
komercijalnog seta za tipizaciju 25 polimorfizama jednog nukleotida (SNP) metodom lančane
reakcije polimerazom i početnica specifičnih za određeni polimorfizam (PCR-SSP). Između 33
para primatelj-nesrodni davatelj, 25 (75,8%) parova imalo je nepodudarnost u HLA gama bloku.
Veći broj nepodudarnosti (≥3) u HLA gama bloku između primatelja i nesrodnog davatelja
pokazao je statistički značajno veću pojavu GvHD-a (p=0,0231). Pozicija SNP 11 u HLA gama
bloku bila je najčešće uočena nepodudarnost (40,0%) i pokazala je značajan utjecaj na pojavu
GvHD-a (p=0,0189).

Abstract (english)

Human Leukocyte Antigen (HLA) genes are routinely typed for allogeneic hematopoietic stem cell
transplantation (HSCT). For that purpose, HLA-A, -B, -C, -DRB1 and -DQB1 loci are tested. HLA
gene mismatch is the main risk factor for undesirable HSCT outcomes. Despite classical HLA gene
matching, mismatches are possible within other genes of the HLA region. In the present study,
association between polymorphisms in the HLA gamma block and the occurrence of Graft versus
Host Disease (GvHD) was studied within a group of 33 patient-unrelated donor pairs. All
individuals were tested for 25 Single Nucleotide Polymorphisms (SNPs) located in the C4 gene
within HLA gamma block using Polymerase Chain Reaction-Sequence Specific Primers (PCRSSP) method. Among 33 patient-unrelated donor pairs, 25 (75.8%) had a mismatch within the HLA
gamma block. The higher number of mismatches (≥3) in the HLA gamma block showed a
significantly higher risk of GvHD occurrence (p=0,0231). SNP position 11 appeared most often
(40.0%) and showed a significant impact on GvHD occurrence (p=0,0189).

• Keywords: alogenična TKMS; HLA gama blok; gen C4; GvHD; SNP
• Keywords (english): allogeneic HSCT; HLA gamma block; C4 gene; GvHD; SNP
• Language: croatian
• URN:NBN: urn:nbn:hr:217:911131
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2024-09-21
• Created on: 2023-10-25 10:14:53