An Exploration of the Associations Between Gut and Serum Immunoglobulin A in Infancy and Asthma in Childhood

• Author / Creator

  van der Leek, Aaron

• Introduction

  Early immune maturation and gut microbial composition have a clear impact on the development of asthma and atopy in children. There is a large body of evidence on the association between immunoglobulin A (IgA), asthma, and other atopic diseases. Low secretory Immunoglobulin A (sIgA) (mucosal) levels in infancy have been associated with the development of asthma and atopic disease in childhood. As well, absence of serum IgA is associated with increased risk for asthma. Serum IgA levels have also been shown to be increased in those with food sensitization, despite the levels being normal for their age. In this thesis, we determined if lower levels of the primary gut mucosal immunoglobulin (sIgA) during infancy were associated with the development of asthma and/or wheeze in a large prospective, normal birth cohort. In another cohort from a health administrative database, we determined associations between serum IgA during in relationship to Emergency Department (ED) visits for asthma and/or wheeze (AW) in childhood.

  Objectives

  This thesis aims to determine the relationships between fecal secretory immunoglobulin A and childhood AW (Study 1) and serum IgA and childhood emergency department visits for AW (Study 2). The objective of study 1 was to determine whether infants with low fecal sIgA (vs normal-high) levels in the first few months of life have increased risk for development AW. Study 2 was developed to determine if low serum IgA children is a useful biomarker for future ED visits for AW.

  Methods

  In study 1, 951 infants from the CHILD study sites, Vancouver, Edmonton and Winnipeg were included based on availability of stool samples. A 3-category variable was used: breastfed (any fecal sIgA level), formula fed with low sIgA levels (lowest tertile) and formula fed with normal-high fecal sIgA levels (highest 2 tertiles). Logistic regression models determined the association (Odds Ratio, OR) between low or normal to high fecal sIgA levels in non-breastfed infants and child AW in comparison to breastfed infants, adjusting for confounding factors identified based on a directed acyclic graph to determine the effect of fecal sIgA levels on childhood AW. In study 2, anonymized administrative health data of 9,938 children who had serum IgA levels assessed when they were <=3 years of age between April 1, 2013 and June 30, 2018 was obtained for analysis from Alberta Health Services (AHS) (Alberta, Canada). Multiple logistic regression models determined the association (Odds Ratio, OR) between normal to high serum IgA (top two tertiles compared to the lowest tertile) and child ED visits for AW adjusting for covariates identified by directed acyclic graph.

  Results

  In study 1, when compared to breastfed infants, formula fed infants with low fecal sIgA levels had 2.20 times the odds of having a diagnosis of asthma in the first three years of life (OR: 2.13; 95%CI: 1.03, 4.43) when controlling for confounding factors. Formula fed infants with normal to high fecal sIgA were at increased risk for atopic AW at age 1-3 years (OR: 5.45; 95%CI: 1.69, 17.31) compared to their breastfeed counterparts. In study 2, when compared to infants with low serum IgA levels, infants with normal-high serum IgA levels (ages 1-2) had an adjusted OR of having an ED visit for AW of 1.21 (95%CI: 1.00, 1.46), controlling for confounding factors. Those with normal-high levels (from 2-3 years) also had significantly increased odds of atopic AW (adjusted OR: 1.79 (95%CI: 1.03, 3.09) when compared to those without.

  Conclusion

  Low levels of infant produced fecal sIgA was associated with increased odds of asthma, whereas normal to high levels were associated with increased odds of atopic AW in comparison to breastfed infants. Normal-high levels of serum IgA in the first 3 years of life appear to be associated with ED visits for AW and atopic AW from 1 until age 3. Further studies are needed to define the relationships between, sIgA, serum IgA, and asthma and atopic sensitization which may provide new insight into the development of respiratory disease and atopic illness in childhood. Overall, both serum IgA and secretory IgA may be important biomarkers to aid in early identification and treatment of those prone to develop atopic diseases like asthma.

• Subjects / Keywords

  • Immunoglobulin A
  • Asthma

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-d6w1-m468

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.