CELLULAR AND MOLECULAR IMMUNOPROFILING OF LUPUS PANNICULITIS: ELUCIDATING THE ROLES OF CYTOTOXIC T CELLS, B CELLS, AND COMPLEMENT ACTIVATION
Bibliographic record
Abstract
O023a / #736 Topic: AS07 - Cutaneous Lupus Late-Breaking Abstract ABSTRACT CONCURRENT SESSION 03: INNATE AND ADAPTIVE IMMUNITY IN SLE 22-05-2025 1:40 PM - 2:40 PM Background/Purpose Lupus panniculitis (LP) is a rare manifestation of cutaneous lupus erythematosus characterized by chronic inflammation of subcutaneous white adipose tissue (SWAT). Despite its distinct clinical and histopathological features, the pathomechanisms driving LP remain poorly understood, leading to untargeted therapeutic strategies. This study aimed to elucidate the cellular and molecular mechanisms underlying LP using imaging mass cytometry (IMC) and NanoString nCounter technology to identify immune signatures and gene expression profiles associated with the disease. Methods Biopsies from 8 LP patients and 6 healthy controls (HC) were analyzed. Cell populations and spatial interactions were assessed via IMC, while gene expression profiles were evaluated using NanoString. Results LP lesions demonstrated extensive leukocyte infiltration, predominantly comprising T cells (CD2+) (48%), B cells (CD20+) (14%), and macrophages (15%). T cells exhibited a cytotoxic (CD8+, Granzyme B+) and skin-homing (CLA+) phenotype, with Th1 polarization driven by type II interferon signaling. B cells displayed strong spatial interactions with naïve T cells. Antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages were abundant and engaged in close interactions with cytotoxic T cells. Abundance of immune cells, particularly B cells, T cells, and cytotoxic cells, in LP was confirmed at mRNA level. LP exhibited significant activation of adaptive immune pathways, with upregulation of T and B-cell signaling genes (CD3D, CD8A, CD19) and antigen presentation pathways (MHC class I and II). A Th1-dominant profile, driven by interferon signaling (STAT1, IRF7) and cytotoxic pathways (TRAIL, TNFRSF1B). Innate immunity in LP showed significant upregulation of Toll-like receptor (TLR) signaling genes (TLR1, TLR2, MYD88). Immunometabolism pathways were altered, with upregulation of IDO1, a key enzyme in tryptophan metabolism, while AHR was downregulated. Complement pathways were activated with upregulation of classical components (C1QA, C1QB) and other regulatory changes. Conclusions This study highlights the role of cytotoxic and skin-homing T- and B cell-predominated immune response and complement activation and immunometabolic dysregulation is involved in LP. The findings provide valuable insights into cellular interactions and gene expression profiles, suggesting potential therapeutic targets, including interferon inhibitors, complement regulators, and metabolic modulators, to improve LP management.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".