同种异体移植肿瘤坏死因子β和白细胞介素16多态性影响肝移植后丙型肝炎病毒的复发及严重程度。

Allograft TNFbeta and IL16 polymorphisms influence HCV recurrence and severity after liver transplantation.

作者信息

Kimball Pam, Baker Melissa, Fisher Robert A

机构信息

Department of Surgery, Medical College of Virginia Hospitals at Virginia Commonwealth University, Richmond, VA 23298, USA.

出版信息

Liver Transpl. 2006 Feb;12(2):247-52. doi: 10.1002/lt.20611.

DOI:10.1002/lt.20611

PMID:16447204

Abstract

Hepatitis C (HCV) recurrence after liver transplantation is universal although severity varies. We explored whether certain donor cytokine gene polymorphisms may be useful markers of susceptibility to severe recurrence. Allograft tumor necrosis factor (TNF) beta and interleukin (IL) 16 gene polymorphisms were correlated with l-yr clinical outcome among HCV+ recipients. Recipients of donor TNFbeta(2,2) (n = 8) experienced less recurrence (50% vs. 71%, P < 0.05), less fibrosis (25% vs. 76%, P < 0.01), and less rejection (25% vs. 71%, P < 0.01) than donor TNFbeta(1,1) (n = 19). Recipients of donor TNFbeta(1,2) (n = 27) demonstrated an intermediate picture with less fibrosis (56%, P < 0.01) and less rejection (37%, P < 0.01) than TNFbeta(1,1). Recipients with donor IL16(TC) (n = 22) showed less recurrence (65% vs. 78%, P = 0.05), less fibrosis (53% vs. 67%, P = 0.06), and less rejection (41% vs. 55%, P = 0.06) than IL16(TT) (n = 32) genotype. Recipients of the combination TNFbeta(2,2)/IL16(TC) donor genotype had the most benign clinical outcome with less recurrence (33% vs. 75%, P < 0.01), no fibrosis (0% vs. 50%, P < 0.001), and fewer rejections (33% vs. 75%, P < 0.01) than donor TNFbeta(1,1)/IL16(TT) genotype. In vitro production of cytokines correlated with genotype. Release of soluble TNFbeta for TNFbeta(1,1) vs. TNFbeta(1,2) and TNFbeta(2,2) was 4803 +/- 2142 pg/mL vs. 5629 +/- 3106 (P = not significant [ns]) and 7180 +/- 3005 (P = ns). Release of soluble IL16 for IL16(TT) vs. IL16(TC) was 437 +/- 86 pg/mL vs. 554 +/- 39 (P = 0.06). In conclusion, allograft TNFbeta and IL16 gene polymorphisms may be useful markers to predict the severity of disease recurrence among HCV+ patients after liver transplantation.

摘要

肝移植后丙型肝炎（HCV）复发普遍存在，不过严重程度有所不同。我们探究了某些供体细胞因子基因多态性是否可能是严重复发易感性的有用标志物。同种异体移植物肿瘤坏死因子（TNF）β和白细胞介素（IL）16基因多态性与HCV阳性受者的1年临床结局相关。供体TNFβ(2,2)（n = 8）的受者比供体TNFβ(1,1)（n = 19）的受者复发较少（50%对71%，P < 0.05）、纤维化较少（25%对76%，P < 0.01）且排斥反应较少（25%对71%，P < 0.01）。供体TNFβ(1,2)（n = 27）的受者表现出中间情况，与TNFβ(1,1)相比纤维化较少（56%，P < 0.01）且排斥反应较少（37%，P < 0.01）。供体IL16(TC)（n = 22）的受者比IL16(TT)（n = 32）基因型的受者复发较少（65%对78%，P = 0.05）、纤维化较少（53%对67%，P = 0.06）且排斥反应较少（41%对55%，P = 0.06）。供体基因型为TNFβ(2,2)/IL16(TC)组合的受者临床结局最良性，与供体TNFβ(1,1)/IL16(TT)基因型相比复发较少（33%对75%，P < 0.01）、无纤维化（0%对50%，P < 0.001）且排斥反应较少（33%对75%，P < 0.01）。细胞因子的体外产生与基因型相关。TNFβ(1,1)与TNFβ(1,2)和TNFβ(2,2)相比，可溶性TNFβ的释放分别为4803±2142 pg/mL对5629±3106（P = 无显著差异[ns]）和7180±3005（P = ns）。IL16(TT)与IL16(TC)相比，可溶性IL16的释放分别为437±86 pg/mL对554±39（P = 0.06）。总之，同种异体移植物TNFβ和IL16基因多态性可能是预测肝移植后HCV阳性患者疾病复发严重程度的有用标志物。