Takahashi N, Nishida H, Kato H, Imanishi K, Sakata Y, Uchiyama T
Maternal and Perinatal Center, Tokyo Women's Medical University School of Medicine, Japan.
Lancet. 1998 May 30;351(9116):1614-9. doi: 10.1016/S0140-6736(97)11125-4.
We have seen a number of patients who developed systemic exanthema and thrombocytopenia in the first week of life. Although nearly 100% of the patients were carriers of meticillin-resistant Staphylococcus aureus (MRSA), no clear link between MRSA and this exanthematous disease has yet been made.
20 neonates with exanthema and thrombocytopenia were selected for study. To see whether superantigenic exotoxins from MRSA are involved in the pathogensis of the exanthematous disease, we studied the production of these exotoxins by MRSA isolates from the neonates. We studied the expression of T-cell-receptor Vbeta and CD45RO in T cells taken from four of the neonates. We also analysed the DNA sequences of 16 cloned Vbeta2-positive T-cell-receptor-chain genes taken from two of the neonates.
Although most of the patients recovered within 5 days of onset of the exanthematous disease without any active treatment, two preterm infants died in the recovery phase. All patients showed colonisation by MRSA. The MRSA produced toxic shock syndrome toxin-1 (TSST-1). The number of T cells positive for T-cell-receptor Vbeta2, reactive to TSST-1, was increased in the four patients studied (p<0.0001), and these T cells expressed CD45RO (p=0.0185). None of the Vbeta2 clones had the same junctional sequences.
The polyclonal expansion of Vbeta2-positive T cells in patients colonised by TSST-1-producing MRSA suggests that the pathogenic micro-organism of this neonatal exanthematous disease is S aureus, mainly MRSA, and that in its pathogenesis it activates T cells by TSST-1. Although the pathogenesis of both this exanthematous disease and toxic shock syndrome are fundamentally the same, a diagnosis of toxic shock syndrome cannot be made in this case, based on the clinical criteria for toxic shock syndrome. We propose neonatal toxic-shock-syndrome-like exanthematous disease (NTED) as the name for this disease.
我们见过一些在出生第一周出现全身性皮疹和血小板减少症的患者。尽管近100%的患者是耐甲氧西林金黄色葡萄球菌(MRSA)携带者,但尚未明确MRSA与这种皮疹性疾病之间的联系。
选择20例患有皮疹和血小板减少症的新生儿进行研究。为了观察MRSA的超抗原外毒素是否参与了这种皮疹性疾病的发病机制,我们研究了从新生儿分离出的MRSA菌株产生这些外毒素的情况。我们研究了从4例新生儿获取的T细胞中T细胞受体Vβ和CD45RO的表达。我们还分析了从2例新生儿获取的16个克隆的Vβ2阳性T细胞受体链基因的DNA序列。
尽管大多数患者在皮疹性疾病发作后5天内未经任何积极治疗即康复,但2例早产儿在恢复期死亡。所有患者均显示有MRSA定植。MRSA产生了毒性休克综合征毒素-1(TSST-1)。在研究的4例患者中,对TSST-1有反应的T细胞受体Vβ2阳性的T细胞数量增加(p<0.0001),并且这些T细胞表达CD45RO(p=0.0185)。没有一个Vβ2克隆具有相同的连接序列。
在被产生TSST-1的MRSA定植的患者中,Vβ2阳性T细胞的多克隆扩增表明,这种新生儿皮疹性疾病的致病微生物是金黄色葡萄球菌,主要是MRSA,并且在其发病机制中,它通过TSST-1激活T细胞。尽管这种皮疹性疾病和毒性休克综合征的发病机制基本相同,但根据毒性休克综合征的临床标准,在这种情况下不能做出毒性休克综合征的诊断。我们提议将这种疾病命名为新生儿毒性休克综合征样皮疹性疾病(NTED)。