Povezanost polimorfizma gena za kemokine CXCL9 i CXCL10 s pojavom akutnog odbacivanja jetrenoga presatka [Association between CXCL9 and CXCL10 chemokine gene polymorphisms and acute graft rejection after liver transplantation]

Ostojić, Ana (2019) Povezanost polimorfizma gena za kemokine CXCL9 i CXCL10 s pojavom akutnog odbacivanja jetrenoga presatka [Association between CXCL9 and CXCL10 chemokine gene polymorphisms and acute graft rejection after liver transplantation]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Acute cellular rejection (ACR) is a clinically important event that negatively affects the survival of the graft and the recipient. As potent T cell- chemoattractants, CXCL9 and CXCL10, have been demonstrated to play a central role in the immune response against transplant tissue, leading to ACR. While increased serum concentrations of CXCL9/10 are associated with ACR occurrence, the association between CXCL9/10 single nucleotide polymorphisms (SNPs) and ACR after liver transplantation (LT) remains unknown. SNPs of CXCL9 (rs10336) and CXCL10 (rs3921) were determined by polymerase chain reaction in 215 recipients transplanted due to alcoholic cirrhosis with or without hepatocellular carcinoma. 27.4% recipients were diagnosed with ACR that was defined as biopsy-proven within 6 months after LT. Recipients that developed ACR had significantly higher MELD scores pre-LT and received significantly younger liver grafts. There was no association between CXCL9/10 genotypes and overall incidence of ACR, the severity of ACR and the number of rejection episodes. However, patients with CXCL9 genotype AA developed ACR earlier, suggesting the involvement of CXCL9-mediated processes in ACR development.

Abstract in Croatian

Akutno stanično odbacivanje (ASO) klinički je vrlo značajan događaj koji ugrožava preživljenje i presatka i primatelja jetre. Kemokini CXCL9/10 imaju ključnu ulogu u regrutiranju T-limfocita u presadak te su njihove povišene serumske vrijednosti povezane s pojavom ASO-a. Međutim, moguća povezanost između jednonukleotidnog polimorfizma gena (PG) za kemokine CXCL9/10 i ASO-a nakon transplantacije jetre nije do sada istražena. PG za CXCL9 (rs10336) i CXCL10 (rs3921 i rs8878) određen je polimeraza lančanom reakcijom kod 215 bolesnika koji su transplantirani zbog alkoholne bolesti jetre s hepatocelularnim karcinomom ili bez njega. Dijagnoza ASO-a histološki je utvrđena kod 27,4% bolesnika. Dokazana je povezanost između ASO-a i mlađe životne dobi davatelja te bodovnog sustava MELD. Međutim, istraživanje je utvrdilo da PG za kemokine CXCL9 (rs10336) i CXCL10 (rs3921 i rs8878) nije povezan ni s pojavnosti ASO-a ni sa stupnjem težine ASO-a nakon transplantacije jetre. Ipak, bolesnici s genotipom CXCL9 (rs10336) AA razvili su ASO značajno ranije, što upućuje na sudjelovanje CXCL9 u razvoju ASO-a.

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