Th105 - The Role of CCL21 in Environmental Allergies and Infection-Associated Chronic Illnesses

Abstract Text: Environmental allergies (EA), characterized by recurrent multi-system symptoms triggered by low-dose antigens, significantly impact both individual health and socioeconomic stability. Despite affecting up to 25.6% of the population, the underlying immune mechanisms contributing to EA remain poorly understood. The MIT MAESTRO clinical study investigates immune pathways associated with infection-associated chronic illnesses (IACI)—including chronic Lyme Disease and Long COVID—through cutting-edge techniques such as neurocognitive assessments, pathogen profiling, and genomic sequencing. Within this study, we utilized TruDiagnostic’s analysis platform, which applies Illumina 850k methylation arrays to model protein and metabolite levels. This allowed us to examine methylation patterns and their relationship to EA severity, with the goal of identifying biomarkers and gaining insights into underlying immune mechanisms. EA severity is measured by a composite score across 28 environmental allergy-related questions, such as mold, heat, and fragrances. We observed a significant negative correlation (Spearman ρ = -0.62, p < 0.05), adjusted for age and sex, between CCL21 methylation levels and EA severity. CCL21 is a chemokine that plays a critical role in regulating the migration of immune cells from tissues into lymphatics. It is upregulated in the skin of subjects exposed to irritants, and mice deficient in CCL21 develop a wide range of allergic conditions, including asthma. Our findings suggest that altered methylation of CCL21 may contribute to the development and pathogenesis of EA and its intersection with IACI. Further studies focused on an EA-specific cohort are currently underway to clarify the immune mechanisms involving CCL21 and identify potential therapeutic targets.