ABSTRACT
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that presents with delays in developmental milestones, social impairment, and behavioral difficulties. Treatment relies upon an intensive individualized multidisciplinary medical and therapeutic approach. This case presents a child affected by ASD and other associated conditions, whose care was significantly limited by the effects of social determinants of health, including lack of transportation, housing instability, low income, and most importantly, lack of health insurance. Without universal health coverage, the US healthcare system requires that patients have insurance or pay out-of-pocket to access medical care. It is vital that healthcare providers are able to recognize and address these barriers in order to help pediatric patients and their families navigate a difficult and often inequitable healthcare system. It is also crucial to emphasize the importance of healthcare providers, policymakers, and advocacy organizations to work together to address the systemic barriers that limit access to quality care for children with ASD.
ABSTRACT
BACKGROUND: Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses. METHODS: Eosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation. RESULTS: Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation. CONCLUSIONS: This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.
