Molecular Epidemiologic analysis of familial case including an discordant identical twin of HTLV-I associated myelopathy (HAM)

我们有一例同卵双胞胎的HTLV-I相关性脊髓病(HAM)的结果不一致(一名健康携带者和HAM患者)。通过Tax基因的核苷酸序列分析、淋巴细胞HTLV-I前病毒载量、血清抗HTLV-I抗体效价、外周血细胞自发增殖和人类白细胞抗原(HLA1)分型，对包括这对双胞胎在内的健康携带者和HAM患者进行了调查。1)随机选择20个不同的分子克隆，用套式聚合酶链式反应扩增出Tax基因。18个克隆中有8个在Liam患者的克隆中发现突变。来自载体的所有克隆都发生了突变。2)5个突变具有非同义突变。3)HAM患者HTLV-L前病毒载量明显高于HAM患者。4)HAM患者自发性增殖过度。5)ENV核苷酸序列突变也是双生子HLAIII锚定基序改变的原因。

We have a case of identical twin of discordant outcome (a healthy carrier and HAM patient) of HTLV-I associated myelopathy (HAM). We investigated healthy carriers and HAM patients in this family including this twin by nucleotide sequence analysis of tax gene, viral load of HTLV-I provirus of lymphocytes, titers of serum anti-HTLV-I antibody, spontaneous proliferation of peripheral blood cells, and HLA typing.1) twenty different molecular clones were selected randomly, then tax gene amplified by nested PCR was sequenced. Eight out of 18 showed mutations were found in clones derived from LIAM patient. All clones from carrier showed mutation.2) Five mutations had non-synonymous mutations. One of change found in carrier may explain difference of immunological response to the HLA anchor motif.3) HTLV-l proviral load was significant higher in HAM patients than on carrier.4) Spontaneous proliferation was exaggerated in HAM patients.5) Nucleotide sequence of ENV also showed mutation responsible for change of HLA anchor motif iii carrier of twin.