Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation

Abstract

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT).Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.

Sohlh1 and Lhx8 are prominent biomarkers to estimate the primordial follicle pool in mice

“…The thermal cycler conditions were as follows: 30 s at 95.0 °C for cDNA denatured, followed by 40 cycles of 15 s at 95 °C and 60 °C for the 34 s. Verification of specific product amplification was performed by dissociation curve analysis. The mRNA relative expression was calculated by the 2^ −ΔCt method with Gapdh used as an internal control [ 16 , 17 ].Primer sequences for each gene were listed in Supplementary Table 1 .…”

Assessing Donor Liver Quality and Restoring Graft Function in the Era of Extended Criteria Donors

“…Interestingly, donors with low Nrf2 mRNA levels (n=8) were significantly older than those with high levels, suggesting that older grafts experienced severe IRI 39 and inferior graft quality. Additionally, Resch et al 40 reported that high gene expression of the major histocompatibility complex class 1 related chain A (MICA) mRNA in zero hour biopsies (n=88) was associated with mild graft injury and prolonged graft survival. During LT, MICA had an important role in linking the innate and adaptive immune responses via interacting with NK cells, mucosal-associated invariant T, CD8+T cells, et al 40 miR-22, a regulator of a series of pathways such as cell cycle, metabolism and kinase signaling, is relevant to cell survival, glucose metabolism, and protein translation.…”

“…Additionally, Resch et al 40 reported that high gene expression of the major histocompatibility complex class 1 related chain A (MICA) mRNA in zero hour biopsies (n=88) was associated with mild graft injury and prolonged graft survival. During LT, MICA had an important role in linking the innate and adaptive immune responses via interacting with NK cells, mucosal-associated invariant T, CD8+T cells, et al 40 miR-22, a regulator of a series of pathways such as cell cycle, metabolism and kinase signaling, is relevant to cell survival, glucose metabolism, and protein translation. 41 Khorsandi et al 41 rereported that low expression of graft miR-22 was associated with the incidence of PNF after DCD LT (n=21).…”

Sohlh1 and Lhx8 are prominent biomarkers to estimate the primordial follicle pool in mice

“…Veri cation of speci c product ampli cation was performed by dissociation curve analysis. The mRNA relative expression was calculated by the 2^-ΔCt method with Gapdh used as an internal control [16,17]. Primer sequences for each gene were listed in Supplementary Table 1.…”