Misra Maneesh Kumar, Pandey Shashi Kant, Kapoor Rakesh, Sharma Raj Kumar, Kapoor Rohit, Prakash Swayam, Agrawal Suraksha
Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India; Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
Hum Immunol. 2014 Aug;75(8):833-9. doi: 10.1016/j.humimm.2014.06.005. Epub 2014 Jun 11.
Human leukocyte antigen (HLA)-G is a non-classical major-histocompatibility complex class-I molecule associated with immunosuppressive function. We have evaluated the impact of HLA-G allele associated with untranslated-region (UTR)-haplotype in end stage renal disease (ESRD) and acute allograft rejection (AR) cases. The mRNA levels of different HLA-G isoforms were evaluated in ESRD and AR cases. Subsequently, the total HLA-G mRNA levels and protein concentration were evaluated against its UTR-haplotype among ESRD and AR cases.
Sequence based typing of the promoter region was carried-out to evaluate the impact of HLA-G haplotype in 350 ESRD cases and 300 controls. HLA-G gene expression was evaluated at the transcriptional level using semi-quantitative and quantitative PCR, whereas protein concentration was determined by ELISA among both cases and control.
Increased risk was observed for G01:01:01:03, G01:01:02, G01:06 and G01:05:N haplotypes while G01:01:01:01 and G01:04:01 haplotypes showed a protective effect in ESRD and AR cases. Higher level of soluble HLA-G isoforms (G5 and G6) was observed among ESRD cases. Reduced levels of soluble isoform (G5) and increased levels of membrane bound (G1 and G3) isoforms were found among AR cases, revealing risk association. Decreased HLA-G expression was observed at both mRNA and protein level for G01:01:01:03 and G01:05:N haplotypes in ESRD and AR cases.
These results suggest that the variation in the expression profile of membrane bound and soluble isoforms may modulate the risk for ESRD and AR. UTR-haplotypes appear to be involved in different HLA-G expression patterns at transcriptional and translational levels.
人类白细胞抗原（HLA）-G是一种与免疫抑制功能相关的非经典主要组织相容性复合体I类分子。我们评估了与非翻译区（UTR）单倍型相关的HLA-G等位基因在终末期肾病（ESRD）和急性移植排斥反应（AR）病例中的影响。在ESRD和AR病例中评估了不同HLA-G异构体的mRNA水平。随后，在ESRD和AR病例中针对其UTR单倍型评估了总HLA-G mRNA水平和蛋白质浓度。
对350例ESRD病例和300例对照进行基于序列的启动子区域分型，以评估HLA-G单倍型的影响。使用半定量和定量PCR在转录水平评估HLA-G基因表达，而通过ELISA在病例组和对照组中测定蛋白质浓度。
在ESRD和AR病例中，观察到G01:01:01:03、G01:01:02、G01:06和G01:05:N单倍型的风险增加，而G01:01:01:01和G01:04:01单倍型显示出保护作用。在ESRD病例中观察到可溶性HLA-G异构体（G5和G6）水平较高。在AR病例中发现可溶性异构体（G5）水平降低，膜结合（G1和G3）异构体水平升高，揭示了风险关联。在ESRD和AR病例中，G01:01:01:03和G01:05:N单倍型在mRNA和蛋白质水平均观察到HLA-G表达降低。
这些结果表明，膜结合和可溶性异构体表达谱的变化可能调节ESRD和AR的风险。UTR单倍型似乎在转录和翻译水平参与不同的HLA-G表达模式。
