Laboratory of Genetics, Immunology and Human Pathologies, Faculty of Sciences of Tunis, University ElManar, and Hemophilia Treatment Centre, Aziza Othmana Hospital, Tunisia.
Diagn Pathol. 2011 Jun 17;6:54. doi: 10.1186/1746-1596-6-54.
The development of inhibitors against factor 8 (F8) is the most serious complication of replacement therapy with F8 in children with severe hemophilia. It was suggested that mismatched F8 replacement therapy may be a risk factor for the development of anti-factor F8 alloantibodies. Recently four single nucleotide polymorphisms (SNPs) encoding six distinct haplotypes, designated H1 through H6, were studied in different populations. Two SNPs are components of the A2 and C2 immunodominant-inhibitor epitopes.The aim of this study is to determine the different types of haplotypes in relation with inhibitors developments and their frequencies in our Tunisian hemophiliac population.
95/116 Tunisian patients with hemophilia A undergoing treatment at Hemophilia Treatment Center, Aziza Othmana hospital, participate in this study. Among them only six patients develop inhibitors. The four SNPs were amplified and sequenced.
In a total of 77 patients, we identified the H1, H2, H3 and the infrequent H5 haplotypes. The H1 and H2 haplotypes, which have the same amino acid sequence in the recombinant F8 molecules used clinically, are the most represented with the frequency of 0.763 and 0.157 respectively. This distribution is almost similar to that of Caucasians in which the frequencies are respectively 0.926 and 0.074, whereas it is 0.354 and 0.374 among Subsaharians. Four patients with inhibitors studied here have the H1 haplotype. For one patient who has a large deletion including the exon 10 we can't identify his haplotype. Theses frequencies may explain partially the low level of inhibitors in our patients.
在儿童重度血友病患者中，使用 F8 因子进行替代治疗会导致 F8 因子抑制剂的产生，这是最严重的并发症。有研究表明，不匹配的 F8 因子替代治疗可能是产生抗 F8 因子同种异体抗体的一个危险因素。最近，在不同人群中研究了编码六个不同单倍型的四个单核苷酸多态性（SNP），分别命名为 H1 到 H6。其中两个 SNP 是 A2 和 C2 免疫显性抑制表位的组成部分。本研究旨在确定不同单倍型与抑制剂发展的关系及其在我们突尼斯血友病患者人群中的频率。
95/116 名在阿齐扎·奥塔曼医院血友病治疗中心接受治疗的突尼斯 A 型血友病患者参与了这项研究。其中只有 6 名患者产生了抑制剂。对这四个 SNP 进行了扩增和测序。
在总共 77 名患者中，我们确定了 H1、H2、H3 和罕见的 H5 单倍型。H1 和 H2 单倍型在临床上使用的重组 F8 分子中具有相同的氨基酸序列，其频率分别为 0.763 和 0.157。这种分布与白种人群相似，其中频率分别为 0.926 和 0.074，而在撒哈拉以南非洲人群中则分别为 0.354 和 0.374。这里研究的 4 名抑制剂患者具有 H1 单倍型。对于一名患有包括外显子 10 在内的大片段缺失的患者，我们无法确定他的单倍型。这些频率可能部分解释了我们患者中抑制剂水平较低的原因。
