EXTRACELLULAR VESICLES FROM LUPUS NEPHRITIS PATIENTS INDUCE CHANGES IN THE TRANSCRIPTIONAL PROFILE OF MONOCYTES THAT RESEMBLE SLAN+ MONOCYTES
Bibliographic record
Abstract
PV114 / #325 Poster Topic: AS12 - Genetics, Epigenetics, Transcriptomics Background/Purpose Extracellular Vesicles (EVs) are a source of autoantigens that can be recognized by circulating monocytes and can also form immune complexes. Lupus nephritis (LN) is the most frequent and severe manifestation in patients with systemic lupus erythematosus (SLE). Renal injury is attributed to the deposition of immune complexes in the glomerulus. SLAN+ monocytes, a fraction of non-classical monocytes considered the most inflammatory, have been detected in renal tissue. We analyzed the transcriptional profile and functional characteristics of monocytes and SLAN+/- monocyte fractions circulating in patients with LN and controls. Additionally, we studied the effect of EVs from the plasma of patients on the transcriptional profile of the SLAN- fraction. Methods We included 3 active LN female patients who meet the American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 diagnosis criteria, with lupus nephritis confirmed by kidney biopsy following the International Society of Nephrology/Renal Pathology Society (ISN/RPS) parameters and in the initial phase of treatment and 3 healthy female donors (HD) of similar age in the study. Circulating monocytes SLAN+/- were purified from peripheral blood using FACS sorting. EVs were isolated from plasma using a differential centrifugation protocol. The SLAN- fraction was seeded with the isolated EVs for 6 hours. RNA from circulating monocyte SLAN+/- fractions and post-EV incubation samples was extracted using a commercial column kit. Transcriptomes were assessed by next-generation RNA sequencing on the Illumina Novaseq platform. Differential expression analysis was performed using the DESeq2 package. GeneCodis, GeneAnalytics, and GSEA platforms were employed for functional enrichment analysis of the most significant and differentially expressed genes (p-adj < 0.05 and FC > 1) between SLAN+/- fractions and to explore the effect of the EVs on the transcriptional profile of SLAN- monocytes. Results Gene expression profiling of monocytes from patients identified 51 genes that were differentially expressed between SLAN+ and SLAN-fractions. The SLAN+ monocytes from LN patients exhibited significant molecular changes, reflecting an inflammatory profile and pathways related to cell adhesion and differentiation. In contrast, the SLAN- fraction demonstrated a strong response to IFN-I. Additionally, EVs from LN patients prompted the SLAN- fraction from healthy donors to express 206 genes associated with an inflammatory profile and enriched SLAN+ signature, indicating differentiation potential. Conclusions These findings highlight the pathogenic potential of SLAN+ monocytes and EVs in lupus nephritis, suggesting they may serve as therapeutic targets. By altering the transcriptional profile of monocytes, EVs from LN patients could contribute to disease progression and inflammation. Targeting these pathways may offer new strategies for intervention in lupus nephritis.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".