Discussion
In this study, we demonstrated that infants with higher cord blood
soluble FasL levels had a higher risk of developing allergic rhinitis,
atopy, and airway obstruction. Cord blood soluble FasL levels were
associated with FeNO and Dermatophagoides pteronyssinus -specific
IgE levels at 7 years old. This indicates that soluble FasL at birth or
during pregnancy has a long-term effect on the development of allergic
diseases in children.
Serum soluble FasL levels have been associated with allergic diseases in
several previous cross-sectional studies. During the allergy season,
serum soluble FasL levels were higher in children with allergic
rhinitis. This was especially true in those with concomitant
asthma.11 During acute asthma exacerbations, children
had significantly higher soluble FasL levels.20 In
adult asthmatic patients, Fas ligand expression was enhanced in
bronchial lavage fluid-derived T-cells after a segmental allergen
challenge.10 Cord blood soluble FasL has also been
associated with atopic dermatitis in 2-year-old children in a nested
case-control study.12
Traditionally, the Fas-FasL interaction that induces apoptosis plays a
role in the disease pathophysiology of conditions such as Steven-Johnson
syndrome and toxic epidermal necrolysis.21 However,
soluble FasL also actively participates in inflammation. Patients with
systemic lupus erythematosus (SLE) have higher soluble FasL levels.
Unlike membrane-bound FasL, the soluble FasL from SLE patients failed to
trigger apoptosis. Instead, the soluble FasL promoted T-cell migration
and caused inflammation via the NF-κB and PI3K
pathways.9,22 Soluble FasL also promoted T-helper 17
lymphocyte migration8 and induced the synthesis of
proinflammatory cytokines and chemokines such as interleukin (IL)-6,
IL-8, and C-X-C Motif Chemokine Ligand 1.23 To the
best of our knowledge, no literature has been able to investigate the
detailed mechanisms surrounding soluble Fas ligand in allergic diseases.
Therefore, the link between cord blood soluble FasL with allergic
outcomes is worthy of further investigation.
This study is limited by the fact that the PATCH birth cohort study is a
relatively small cohort. The results found in this research need to be
confirmed by larger birth cohorts. Another limitation is that a high
percentage of participants either voluntarily withdrew from the study or
have been lost to follow-up. The latter is a common challenge in many
birth cohort studies. However, the follow-up rate of the PATCH birth
cohort study was comparable to those of other birth cohorts that also
included serial blood samplings and lung function
testing.24,25
The strength of this study lies in being a longitudinal cohort that
enrolled the general population rather than only newborns at high risk.
Moreover, the atopic outcomes were ensured to be accurate since the
diagnosis of asthma and other atopic diseases were based on long-term
histories and made by pediatric allergists and pulmonologists. The
diagnosis of asthma was also facilitated by the objective parameters
derived from the lung function and FeNO tests.
In conclusion, higher cord blood soluble FasL levels at birth have a
potential long-term effect on atopic diseases, allergen sensitization,
and lung function. This association indicates that the cord blood
soluble FasL level at birth may be used as a biomarker to predict the
probable development of allergic diseases later in life.