{
  "abstract": "Lupus nephritis (LN) develops in 40–60% of patients with systemic lupus erythematosus (SLE) and remains the leading cause of renal morbidity and progression to end-stage renal disease (ESRD). While the upstream immunological events initiating LN—including loss of self-tolerance, pathogenic autoantibody production, glomerular immune complex deposition, and type I interferon (IFN) activation—are broadly shared, accumulating evidence demonstrates that these convergent triggers give rise to molecularly heterogeneous tissue injury programs at the renal level. This fundamental divergence provides a mechanistic explanation for the inconsistent therapeutic responses observed with standardized immunosuppressive protocols. Advances in single-cell transcriptomics, spatial gene expression mapping, CITE-seq, and cross-platform multi-omic integration have deconvolved this heterogeneity into at least five recognizable tissue-level injury programs: (i) an IFN-γ-polarized macrophage–tubular epithelial cell co-activation circuit, (ii) a Tfh–B cell ectopic germinal center pathway, (iii) a neutrophil extracellular trap (NET)-driven inflammatory cascade, (iv) a podocyte-autonomous injury program, and (v) a TREM2+ macrophage-orchestrated fibrotic program. Concurrently, multiplexed urinary biomarker platforms are under development as non-invasive surrogates for tissue-level pathogenic activity. This review synthesizes current understanding of disease mechanisms, molecular profiling evidence, biomarker candidates, and mechanism-directed therapies corresponding to each tissue injury program. We map existing and investigational agents—including anifrolumab, obinutuzumab, voclosporin, CAR-T cell therapy, and complement inhibitors—to their mechanistic targets and delineate the design requirements for prospective biomarker-stratified trials essential to validating molecularly guided treatment selection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine",
    "Department of Traditional Chinese Medicine, Gaoxin Branch of the First Affiliated Hospital, Nanchang University"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jun Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Xiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Jian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/30qejrey0qwg5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1987126",
  "fulltext_url": "https://europepmc.org/articles/PMC13714975",
  "id": "30qejrey0qwg5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1987126/full",
  "language": "eng",
  "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": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W7221835879",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1987126/pdf",
  "pmcid": "PMC13714975",
  "pmid": "42953253",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/30qejrey0qwg5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1987126",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1987126/full"
    },
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953253",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953253"
    },
    {
      "first_seen": "2026-11-01T12:22:22Z",
      "native_id": "PMC13714975",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1987126"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Decoding molecular heterogeneity in lupus nephritis: integrating single-cell and spatial multi-omics for endotype-driven precision therapeutics",
  "title_text": "Decoding molecular heterogeneity in lupus nephritis: integrating single-cell and spatial multi-omics for endotype-driven precision therapeutics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:22Z",
  "url": "https://research.draconitic.com/paper/30qejrey0qwg5",
  "venue": "Frontiers in Immunology",
  "versions": []
}