Gul Kiran Aftab, Sonerud Tonje, Fjærli Hans O, Nakstad Britt, Abrahamsen Tore Gunnar, Inchley Christopher S
Department of Pediatric Research, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Department of National Newborn Screening, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway.
BMC Infect Dis. 2017 Jan 5;17(1):18. doi: 10.1186/s12879-016-2148-0.
Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in previously healthy infants. Immunological mechanisms predisposing infants to severe disease are poorly understood. Early biomarkers for disease severity may assist clinical decisions. We investigated T-cell receptor excision circles (TREC), episomal DNA made during thymic T-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for RSV disease severity.
One hundred thirteen patients hospitalized with RSV infection <12 months of age, grouped by disease severity, were available for this investigation, in which we conducted both a prospective and a case-control study. The prospective study included 47 RSV positive infants (mild n = 13, moderate n = 10, severe n = 24). TREC counts were determined by PCR of DNA extracted from EDTA-blood collected on hospitalization, and corrected for lymphocytes using ANCOVA. The case-control study included 85 newborns who later in infancy became RSV positive (mild n = 32, moderate n = 24, severe n = 29) and 47 newborns who never developed RSV disease as healthy controls included from health centres in the same catchment area. TRECs were measured using DNA extracted from dry blood spots from stored neonatal screening cards, followed by PCR. Student's T-test compared patients with controls, ANOVA compared disease severity groups.
During RSV infection patients in the severe disease group had significantly lower (p = 0.017) TREC/200 μL blood compared to the other two disease groups, after correction for lymphocyte count. Newborn TREC levels, were significantly higher in RSV patients compared to controls (p < 0.0001). No significant differences in TREC copies at birth were found between disease severities.
During acute RSV infection a lower number of TREC is found in the severe disease group. TREC has potential as an immunological marker for severe RSV infection. Higher neonatal TREC counts indicate that infants later presenting with severe RSV do not have reduced thymic activity at birth and probably no congenital T-cell defect.
呼吸道合胞病毒（RSV）感染是既往健康婴儿住院的重要原因。导致婴儿患重症疾病的免疫机制尚不清楚。疾病严重程度的早期生物标志物可能有助于临床决策。我们研究了T细胞受体切除环（TREC），即胸腺T细胞受体重排过程中产生的游离DNA，以及胸腺活性标志物，在疾病期间以及新生儿筛查卡片中作为RSV疾病严重程度的危险因素。
113例年龄小于12个月因RSV感染住院的患者，按疾病严重程度分组，可用于本研究，我们进行了一项前瞻性研究和一项病例对照研究。前瞻性研究包括47例RSV阳性婴儿（轻度n = 13，中度n = 10，重度n = 24）。通过对住院时采集的EDTA血样中提取的DNA进行PCR测定TREC计数，并使用协方差分析对淋巴细胞进行校正。病例对照研究包括85例婴儿期后期RSV呈阳性的新生儿（轻度n = 32，中度n = 24，重度n = 29）和47例从未患RSV疾病的新生儿作为来自同一集水区健康中心的健康对照。使用从储存的新生儿筛查卡片干血斑中提取的DNA，然后进行PCR来测量TREC。学生t检验比较患者与对照，方差分析比较疾病严重程度组。
在RSV感染期间，校正淋巴细胞计数后，重症疾病组患者每200μL血液中的TREC显著低于其他两个疾病组（p = 0.017）。与对照组相比，RSV患者的新生儿TREC水平显著更高（p < 0.0001）。疾病严重程度之间在出生时TREC拷贝数上未发现显著差异。
在急性RSV感染期间，重症疾病组中发现的TREC数量较少。TREC有潜力作为严重RSV感染的免疫标志物。新生儿TREC计数较高表明，后来出现严重RSV的婴儿出生时胸腺活性没有降低，可能也没有先天性T细胞缺陷。
