Rathore Deepak K, Nair Deepa, Raza Saimah, Saini Savita, Singh Reeta, Kumar Amit, Tripathi Reva, Ramji Siddarth, Batra Aruna, Aggarwal Kailash C, Chellani Harish K, Arya Sugandha, Bhatla Neerja, Paul Vinod K, Aggarwal Ramesh, Agarwal Nidhi, Mehta Umesh, Sopory Shailaja, Natchu Uma Chandra Mouli, Bhatnagar Shinjini, Bal Vineeta, Rath Satyajit, Wadhwa Nitya
Pediatric Biology Centre, Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
PLoS One. 2015 Apr 21;10(4):e0123589. doi: 10.1371/journal.pone.0123589. eCollection 2015.
While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation.
In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself.
An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance.
These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.
在印度,感染是新生儿死亡的主要原因,即使是足月儿也是如此,而对于很大比例(约20%)出生时体重过轻(或小于胎龄;SGA)的新生儿来说,这更是一个特殊问题。这种易感性的一个潜在促成因素可能是免疫系统成熟可能会随着宫内生长迟缓而受到影响。
为了研究免疫状态差异可能是SGA新生儿易感染的基础这一可能性,我们对足月SGA新生儿脐带血中的22种白细胞亚群的频率和浓度以及IgM和IgA水平进行了计数,并将其与正常体重(或适于胎龄;AGA)足月新生儿的值进行比较。我们在排除标准中消除了大多数与SGA相关的危险因素,以确保AGA与SGA之间的差异(如果有的话)更可能与体重过轻状态本身相关。
对502份此类样本(包括50份SGA新生儿样本)的分析表明,与AGA新生儿相比,SGA新生儿脐带血中的浆细胞样树突状细胞(pDC)明显较少,髓样树突状细胞(mDC)与pDC的比例较高,自然杀伤(NK)细胞较多,IgM水平较高。还观察到了其他差异,如CD4:CD8比值有降低的趋势,炎症单核细胞、mDC和中性粒细胞更为突出,但其中一些差异虽大,但未达到统计学意义的标准水平。
免疫系统细胞谱系的这些差异可能反映了与生长受限相关的宫内应激反应。因此,对感染易感性增加可能与复杂的免疫系统失调有关,而不仅仅是免疫系统成熟迟缓。