IL-33/ST2 signaling pathway: preliminary study to assess its role in Chronic rejection after liver transplant

ARRIOLA BENITEZ PC; PÉREZ ILLIDGE L; MOREIRA J; CASTRO A; FERNANDEZ MF; TIRIBELLI C; DESCALZI V; RUMBO MARTIN; GENTILINI MV; G, GONDOLESI

Congreso; 29th International Congress of The Transplantation Society (TTS 2022); 2022

Introduction: The improvements in the immunosuppression therapies have reduced the prevalence of chronic rejection (CR) of liver allografts, however CR still represents an important cause of graft loss requiring re-transplantation. The biological mechanisms underlying this process remained not completely understood. IL-33 and its receptor (ST2) play important roles in the immune regulatory pathways including tolerance and cirrhosis development and virus infection. To the best of our knowledge, no reports are available describing its role after liver transplant (LT).Objective: Studying the IL-33/ST2 axis in CR after liver transplant in humans. Methodology: Liver tissue samples obtained at the time of liver transplantation from donors (Control Group, n=9) and liver tissue obtained from LT (n=12) patients were include in the study. Samples were retrospectively pooled into three groups: NR (No Rejection, normal without any histopathological signs of rejection, n=4), NR-LD (without any histopathological signs of rejection, but presenting liver disease of different causes (i.e., toxic damage, n=5) and CR (chronic rejection, with positive histopathological findings, n=3). Comparisons analysis was made using the Kruskal–Wallis with Dunn’s post-test. Correlations were evaluated with the Spearman rank correlation test. The present protocol was approved by the Institutional Review Board of HUFF (DDI [1490] 2419). Results: Hepatic levels of IL33 were not statistically different among groups. Nevertheless, the expression of ST2 was significantly higher in liver samples obtained from patients in CR and NR-LD groups (p< 0.05) (Figure 1). Then, we investigated whether ST2 levels were associated with hepatocellular and cholestatic damage, finding that ST2 correlated positively with TB, AST, ALT and ALP levels (p