Chemical cartography identifies potential mechanistic, diagnostic, and therapeutic opportunities in RAG deficiency
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: ) in humans drive an array of immunodeficiencies with non-continuous symptom patterns. Previous multi-omic studies identified immune cell types and cytokines that defined RAG subtypes, but mechanisms remain to be established. Objective: -mutated patients. Method: -mutated patient and healthy control plasma was analyzed across two cohorts using a chemical cartography approach wherein oxidative, dysbiotic, energetic, and neuroimmune patterns were broadly targeted through a series of overlaid immunometabolic and immunolipidomic profiling methods. Results: Patterns in tryptophan metabolism, purine metabolism, lipid stress molecules, and oxylipin products of 12-lipoxygenase segregated disease subtypes and presented potential targets in RAG-disease pathology. Purine metabolism and certain lipid oxidation phenotypes were exacerbated after hematopoietic stem cell transplantation, suggesting continuing pathology after treatment. Conclusions: This investigation reveals potentially targetable immune-related metabolic and lipidomic correlates of disease heterogeneity in human RAG-deficiency.
Source: Frontiers in Immunology
Authors: Gwendolyn Cooper, Ottavia M. Delmonte, Ian S. LaCroix, Dimana Dimitrova, Marita Bosticardo, Heather Kenney, Gloria Magro, Francesca Pala, Zixiao An, Jenna R. E. Bergerson, Alexandra F. Freeman, Jennifer R. Heimall, Steven M. Holland, Danielle Fink, Douglas B. Kuhns, Nathan T. Brandes, Eric Bohrnsen, Jade Uriarte, Benjamin Schwarz, Luigi D. Notarangelo
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223290205