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Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus
Sree Nethra Bulusu1, Anitha Nagaraj Bavikatte2, Sanket Shah1
1Department of Clinical Immunology, Jawaharlal Institute of Post-Graduate Medical Education and Research (JIPMER), Puducherry, India.
Immunology
|January 28, 2025
Summary
This study reveals key gene expression differences in lupus nephritis (LN) patients who did not respond to cyclophosphamide (CYC) treatment. Identifying these biomarkers can help predict non-response and renal flare, improving patient outcomes.
Area of Science:
- Immunology
- Genomics
- Nephrology
Background:
- Lupus nephritis (LN) treatment non-response mechanisms remain unclear.
- Understanding molecular differences in responders versus non-responders is crucial for therapeutic advancement.
Purpose of the Study:
- To characterize the transcriptome of peripheral blood mononuclear cells (PBMCs) and renal tissues in LN patients before and after cyclophosphamide (CYC) treatment.
- To identify molecular markers that predict treatment response, non-response, and renal flare.
Main Methods:
- Paired PBMCs and renal tissues from 16 proliferative LN patients were sequenced before and after CYC treatment.
- Transcriptomic analysis included comparative analyses, weighted gene co-expression network analysis (WGCNA), and ROC analysis.
Main Results:
- Distinct transcriptomic pathways were identified for clinical responders (CR), non-responders (NR), and patients who flared (FL).
- In NR PBMCs, ECM molecules and BCR signaling were upregulated; in NR renal tissue, TLR, IFN, and NF-κB signaling were upregulated.
- TENM2, NLGN1, and AP005230.1 from PBMCs, and AP005230.1 from renal tissue, predicted non-response with high AUC values. AC092436.3 from PBMCs predicted renal flare.
Conclusions:
- Significant differentially expressed genes (DEGs) and pathways correlate with specific treatment outcomes in LN.
- Hub genes TENM2, NLGN1, AP005230.1, and AC092436.3 serve as potential biomarkers for predicting non-response and renal flare in LN patients treated with CYC.
