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.