Neonatal Dysregulated Immune Function and Pediatric B-Cell Precursor ALL


Key Points

  • Children with B-cell precursor ALL are born with abnormal concentrations of inflammatory markers.
  • This observation supports the hypothesis that children with ALL have a dysregulated immune function that is detectable at birth.
  • Children who develop ALL could potentially react abnormally to infections in early childhood.

A high incidence of clinically diagnosed infections in the first year of life among children who later developed acute lymphoblastic leukemia (ALL) has led researchers to propose that children with ALL are born with a dysregulated immune function, resulting in a more vigorous reaction to infections during early childhood. To assess the association between neonatal concentrations of inflammatory markers and the risk of developing childhood ALL, Søegaard et al conducted a population-based case-control study of children who were diagnosed with B-cell precursor ALL and matched controls. The study found neonatal concentrations of eight detectable markers that were significantly different in children later diagnosed with ALL compared with the control group. The study’s findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function. The study was published in Cancer Research.

Study Methodology

The researchers used data from Denmark’s Neonatal Screening Biobank and nationwide registers to assess baseline characteristics of the immune system of children born in Denmark between 1995 and 2008. The researchers measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at between age 1 and 9 were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with these nationwide registers, the researchers also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL.

Study Findings

The researchers found that children who developed B-cell precursor ALL had significantly lower neonatal concentrations of interleukin-8 (IL-8), soluble IL-6 receptor (sIL-6Ra), transforming growth factor (TGF)-β1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP). They also had higher concentrations of IL-6, IL-17, and IL-18 than did matched controls. Concentrations of IL-10 were below the detection level for both patients and controls.

Birth order (IL-18 and CRP), gestational age (sIL-6Ra, TGF-β1, and CRP), and sex (sIL-6Ra, IL-8, and CRP) were significantly associated with the neonatal concentrations of inflammatory markers, but maternal age, infections during pregnancy, birth weight, and mode of delivery were not associated.

“Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function,” concluded the researchers.

“Our findings underline the role the child’s baseline immune characteristics may play in the development of ALL," said Signe Holst Søegaard, MSc, PhD, a fellow in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, Denmark, and lead author of this study. “However, we cannot yet use our research results to predict who will develop childhood ALL. In future studies, we will further characterize the relation between immune constitution at birth and risk of childhood ALL with the ultimate goal of developing preventive strategies targeting predisposed children.”

Dr. Søegaard is the corresponding author of this study.

Funding for this study was provided by the Dagmar Marshall Foundation, the A.P. Møller Foundation, the Danish Childhood Cancer Foundation, the Arvid Nilsson Foundation, and the Danish Cancer Research Foundation.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.