Westhoff Connie M, Vege Sunitha, Wylie Dwane, Nickle Pam, Lomas-Francis Christine, Hue-Roye Kim, Reid Marion E
Molecular Blood Group and Platelet Testing Laboratory, American Red Cross, Penn-Jersey Region, Philadelphia, PA 19130, USA.
Transfusion. 2009 Apr;49(4):725-32. doi: 10.1111/j.1537-2995.2008.02034.x. Epub 2008 Dec 23.
The JAL antigen (Rh48) was discovered more than 30 years ago when it caused hemolytic disease of the fetus and newborn in an African American family. A decade later it was found to cause hemolytic disease of the fetus and newborn in a Caucasian family. The presence of the same low-prevalence antigen in two different ethnic groups is rare, but additional JAL+ in both groups was subsequently identified. This study was undertaken to investigate the RH gene(s) responsible for expression of JAL and to determine the structural relationship between JAL and other Rh antigens.
Samples from 17 JAL+ people were included: 2 Caucasian, 6 African American, 7 African Brazilian, 1 Caribbean, and 1 Puerto Rican. RHCE and RHD were investigated at the genomic level, and Rh cDNAs were cloned and sequenced for some samples.
Caucasian JAL+ probands had RHCECe, while JAL+ probands with African ancestry had RHCEce, but all had a nucleotide 340C>T change in Exon 3 of RHCE predicted to encode Arg114Trp. The JAL-encoding RHCEce also had 733C>G (Leu245Val) and was linked to conventional RHD or to RHDDAU0.
JAL+ results from a nucleotide 340C>T (Arg114Trp) on either a Ce or ce background. Homology modeling of the JAL+ RhCE protein suggests that the Arg-->Trp change eliminates a critical loop-stabilizing H-bond between the side chain of Arg114 and the e-specific amino acid Ala226. Additionally, accommodation of the bulky tryptophan would disrupt the conformation of the extracellular loops containing C/c- and e-specific amino acids, providing a structural hypothesis for the simultaneous altered expression of C/c, e, and V/VS antigens.
JAL抗原（Rh48）于30多年前被发现，当时它在一个非裔美国家庭中引发了胎儿及新生儿溶血病。十年后，在一个白种人家庭中也发现它会导致胎儿及新生儿溶血病。在两个不同种族群体中出现相同的低频率抗原是很罕见的，但随后在这两个群体中都发现了更多JAL阳性个体。本研究旨在调查负责JAL表达的RH基因，并确定JAL与其他Rh抗原之间的结构关系。
纳入了17名JAL阳性个体的样本，其中包括2名白种人、6名非裔美国人、7名非洲裔巴西人、1名加勒比人以及1名波多黎各人。在基因组水平上研究了RHCE和RHD，并对一些样本的Rh cDNA进行了克隆和测序。
白种人JAL阳性先证者的RHCE基因为Ce，而有非洲血统的JAL阳性先证者的RHCE基因为ce，但所有个体在RHCE外显子3中都有一个核苷酸340C>T的变化，预计编码精氨酸114变为色氨酸。编码JAL的RHCEce还存在733C>G（亮氨酸245变为缬氨酸），并与传统的RHD或RHDDAU0连锁。
JAL阳性是由Ce或ce背景上的核苷酸340C>T（精氨酸114变为色氨酸）导致的。JAL阳性RhCE蛋白的同源性建模表明，精氨酸到色氨酸的变化消除了精氨酸114侧链与e特异性氨基酸丙氨酸226之间一个关键的稳定环的氢键。此外，庞大的色氨酸的容纳会破坏包含C/c和e特异性氨基酸的细胞外环的构象，为C/c、e和V/VS抗原同时改变的表达提供了一个结构假说。
