{
  "abstract": "Background: Mutations in the recombination-activating genes (RAG1 and RAG2 ) 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.\n\nObjective: To use circulating metabolic and lipidomic patterns to further resolve drivers of symptom heterogeneity and suggest alternative therapeutic targets in RAG -mutated patients.\n\nMethod: RAG -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.\n\nResults: 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.\n\nConclusions: This investigation reveals potentially targetable immune-related metabolic and lipidomic correlates of disease heterogeneity in human RAG-deficiency.",
  "abstract_shown": true,
  "affiliations": [
    "Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health",
    "Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health",
    "Center for Immuno-Oncology, National Cancer Institute, National Institutes of Health",
    "Division of Allergy and Immunology, Children’s Hospital of Philadelphia",
    "Neutrophil Monitoring Lab, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gwendolyn Cooper"
    },
    {
      "affs": [
        1
      ],
      "name": "Ottavia M. Delmonte"
    },
    {
      "affs": [
        0
      ],
      "name": "Ian S. LaCroix"
    },
    {
      "affs": [
        2
      ],
      "name": "Dimana Dimitrova"
    },
    {
      "affs": [
        1
      ],
      "name": "Marita Bosticardo"
    },
    {
      "affs": [
        1
      ],
      "name": "Heather Kenney"
    },
    {
      "affs": [
        1
      ],
      "name": "Gloria Magro"
    },
    {
      "affs": [
        1
      ],
      "name": "Francesca Pala"
    },
    {
      "affs": [
        1
      ],
      "name": "Zixiao An"
    },
    {
      "affs": [
        1
      ],
      "name": "Jenna R. E. Bergerson"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexandra F. Freeman"
    },
    {
      "affs": [
        3
      ],
      "name": "Jennifer R. Heimall"
    },
    {
      "affs": [
        1
      ],
      "name": "Steven M. Holland"
    },
    {
      "affs": [
        4
      ],
      "name": "Danielle Fink"
    },
    {
      "affs": [
        4
      ],
      "name": "Douglas B. Kuhns"
    },
    {
      "affs": [
        0
      ],
      "name": "Nathan T. Brandes"
    },
    {
      "affs": [
        0
      ],
      "name": "Eric Bohrnsen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jade Uriarte"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Schwarz"
    },
    {
      "affs": [
        1
      ],
      "name": "Luigi D. Notarangelo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ahvx3qwbxy3eg.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1960496",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960496/full",
  "id": "ahvx3qwbxy3eg",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960496/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC581-607"
    ],
    [
      "openalex",
      "2403|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7223290205",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1960496/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ahvx3qwbxy3eg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1960496",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960496/full"
    },
    {
      "first_seen": "2026-10-30T13:43:11Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "Chemical cartography identifies potential mechanistic, diagnostic, and therapeutic opportunities in RAG deficiency",
  "title_text": "Chemical cartography identifies potential mechanistic, diagnostic, and therapeutic opportunities in RAG deficiency",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:11Z",
  "url": "https://research.draconitic.com/paper/ahvx3qwbxy3eg",
  "venue": "Frontiers in Immunology",
  "versions": []
}