DISTINCT CELL-BOUND COMPLEMENT ACTIVATION PRODUCTS ASSOCIATE WITH DISEASE ACTIVITY AND IMMUNE TRANSCRIPTIONAL SIGNATURES IN SLE
Bibliographic record
Abstract
PV116 / #181 Poster Topic: AS14 - Innate Immunity Background/Purpose Complement plays a central role in SLE, generating an array of bioactive soluble and cell-bound complement activation products (CB-CAPs) during disease activity. Data are lacking though detailing the types, quantities, and impacts of the numerous CB-CAP on SLE immune cells, especially with respect to disease activity. We applied a mass cytometry (MC) panel that can detect over 20 CB-CAPs and complement receptors to PBMCs from paired flare and remission samples from 6 patients with classified SLE. Furthermore, we analyzed single-cell transcriptional profiles on flaring samples using antibodies to the most prevalent CB-CAPs using cellular indexing of transcriptomes and epitopes (CITE)-seq. Methods Adults with ACR- or SLICC-classified SLE were consented for PBMC collection at Washington University School of Medicine. Isolated PBMCs were subjected to single-cell MC (n = 6) and CITE-seq (n = 3). MC data analysis was performed with Cytobank. CITE-seq data analyses was performed with Seuret, gProfileR, and Comprehensive Multi-omics Platform for Biological InterpretatiOn (COMPBIO). Results We found the highest frequency of C4d, C3d, C5, and Bb deposition on B cells compared to T cells and monocytes during SLE flares (Figure 1). During disease remission, low levels of all CB-CAPs were observed in these cells. Compared to controls, transitional B cells from flaring patients with SLE had high levels of C5 and Bb with little C4d or C3d. CD11c + B cells from flaring patients also had elevated Bb deposition compared to controls. CITE-seq transcriptional profiling identified Bb- and C3d-bearing CD11c + B cells possessing a type I interferon signature, with Bb-bearing B cells further possessing a TNF/NF-κB transcriptional signature (Figure 2). Figure 1. Figure 2. Conclusions A high level of CB-CAP deposition was observed in B cells obtained from flaring subjects with a SLE, which was absent during disease remission. The types of CB-CAPs found on PBMCs were not uniform between cell types, potentially opening a previously undescribed heterogeneity in SLE. Additional heterogeneity was observed in the transcriptional profiles associated with specific CB-CAPs on B cells. These pilot data demonstrate the feasibility of the MC complement panel on human samples, and the potential insights CITE-seq has using CB-CAPs in discovering novel mechanisms of complement activation and regulation.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".