NFLUENCE OF PATIENT AND DONOR MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) 173 G/C, INTRACELLULER ADHESION MOLECULE 1 (ICAM-1) G241R POLYMORPHISM ON LIVER ALLOGRAFT REJECTION: EVIDENCE FROM A SING
Makaleler > Tam Makale · 2005
Yazarlar: C Arikan, A Berdeli, M Kilic, R Yagci, Sema AYDOĞDU
Journal of Pediatric Gastroenterology and Nutrition, Uluslararası, Wos, 2005, cilt 40, ss 673-673
DOI: 10.1097/00005176-200505000-00180
Özet
Background: Cytokines are key immune mediators and it has been suggested that cytokine gene polymorphisms affecting expression influence rejection or tolerance. Macrophage migration inhibitory factor is a proinflammatory cytokine that plays role in cell mediated immunity and delayed type hypersensitivity. MIF expression is upregulated along with another cytokines such as ICAM-1. The significance of these molecules in the pathogenesis of liver allograft rejection and rejection treatment outcome is not clear. Aim: To determine whether an association exists between gene polymorphisms and liver allograft rejection and rejection therapy outcome. Method: Patients who received a primary liver graft from 2000 onward and were seen at the transplant outpatient clinic since then were included on this study. Frequency data for the polymorphisms in the transplanted group (N = 52) and their matched donors, where available (N = 33), were divided into biopsy proven rejectors (n = 8) and non -rejectors (n = 44). They also compared with a group of healthy controls (n = 140). After informed consent, blood sample was collected and DNA was obtained. Using amplification-refractory mutation system polymerase chain reaction, ICAM-G241R and MIF173G/C gene polymorphisms were performed. Rejection grading was assessed according to Banff criteria. Associations were assessed by using Fisher's exact test. Results: Primary indication for liver transplantation was biliary atresia (n= 12), metabolic liver disease (n = 24), autoimmune hepatitis (n = 6) and the others (n = 10). The median age of patients was 7.7 (ranged; 0.5-16 years). Primary immunosuppression consisted of cyclosporine A in 12 patients and FK-506 in 40 children. Clinically diagnosed rejection was observed in 21 children, 8 of whom were biopsy-proven acute rejection. Median rejection time was 11 days (ranged 6-121). Rejectors most often showed the GG or AG genotype, whereas no rejectors possessed the AA genotype. Univariate analysis showed that polymorphism of ICAM-G241R was significantly related to liver graft rejection. No significant difference was observed in the presence of any genotypes of recipient and donor MIF be tween nonrejectors and rejectors (p = 0.44 and p = 0.27, respectively). When patients were analyzed according to biopsy proven rejectors and non rejectors, we found that polymorphism of recipient and donor ICAM-G241R was significantly correlated to allograft rejection (p = 0.05 and p = 0.05) respectively. The donors whose recipients did not develop rejection had a significant increase of ICAM-G241R GG genotype compared with donors, whose recipients developed rejection episode. On the other hand rejector recipients did not have ICAM-G241R AA genotype compared to nonrejectors. Despite steroid responsive rejectors (n = 13) had more MIF GC genotype than steroid nonresponsive rejectors (n = 8), it did not reach statistically significance (%87.5 vs. %12.5; p = 0.056). Conclusion: There is a relationship between a genetic characteristics and susceptibility to rejection after liver transplantation. According to our preliminary result, recipient ICAM-G241R AA and donor ICAM-G241R GG genotype has preventive role for acute liver allograft rejection. MIF genotype detection may be useful to estimate patients' response to steroid therapy in acute liver allograft rejection.