Colobran R, Casamitjana N, Roman A, Faner R, Pedrosa E, Arostegui J I, Pujol-Borrell R, Juan M, Palou E
Laboratori d'Immunobiologia per a la Recerca i Aplicacions Diagnòstiques, Banc de Sang i Teixits, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
Genes Immun. 2009 Apr;10(3):254-9. doi: 10.1038/gene.2008.96. Epub 2009 Jan 15.
Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n=161). Patients with no acute rejection showed a significantly lower mean number of CCL4L copies than patients that showed acute rejection (1.66 vs 1.96, P=0.014), with an even greater number of gene copies seen in patients with more than one episode of acute rejection (1.66 vs 2.30, P=0.001). Additionally, patients with > or =2 CCL4L copies had a significantly higher risk of acute rejection compared with patients that had 0-1 CCL4L copies (odds ratio 2.65; 95% confidence interval, 1.33-5.28; P=0.0046). A combined analysis of CCL4L CNV and the rs4796195 CCL4L single nucleotide polymorphism demonstrated that the effect of CCL4L copy number in acute rejection is mainly because of the number of copies of the CCL4L1 allelic variant. This finding constitutes the first report of CNV as a correlate factor in allograft rejection.
肺移植（LT）已成为选定的晚期肺部疾病患者可接受的治疗方法。成功进行LT的主要限制之一是移植器官的排斥反应，其中趋化因子是关键介质。在此，我们测试了CCL4L趋化因子基因的拷贝数变异（CNV）与LT患者（n = 161）排斥风险之间的关系。无急性排斥反应的患者CCL4L拷贝的平均数量明显低于有急性排斥反应的患者（1.66对1.96，P = 0.014），在有不止一次急性排斥反应的患者中观察到的基因拷贝数更多（1.66对2.30，P = 0.001）。此外，与有0 - 1个CCL4L拷贝的患者相比，有≥2个CCL4L拷贝的患者发生急性排斥反应的风险显著更高（优势比2.65；95%置信区间，1.33 - 5.28；P = 0.0046）。对CCL4L CNV和rs4796195 CCL4L单核苷酸多态性的联合分析表明，CCL4L拷贝数在急性排斥反应中的作用主要是由于CCL4L1等位基因变体的拷贝数。这一发现构成了CNV作为同种异体移植排斥反应相关因素的首次报道。
