2024-01-22 ヒューストン大学(UH)
◆研究ではProximity Extension Assay(PEA)と呼ばれる手法を使用し、既存のバイオマーカーに加えて新たに6つのバイオマーカーを同定しました。これにより、ループス患者の治療を早期に始める可能性があります。
<関連情報>
- https://uh.edu/news-events/stories/2024/january/01222024-mohan-lupus-nephritis-new-briomarkers-dna.php
- https://www.sciencedirect.com/science/article/abs/pii/S0896841123001749
近接拡張アッセイプロテオミクスと腎単一細胞トランスクリプトミクスにより、活動性ループス腎炎の新規尿中バイオマーカーが発見される Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis
Yaxi Li, Chenling Tang, Kamala Vanarsa, Nga Thai, Jessica Castillo, Gabrielle Alexis Braza Lea, Kyung Hyun Lee, Soojin Kim, Claudia Pedroza, Tianfu Wu, Ramesh Saxena, Chi Chiu Mok, Chandra Mohan
Journal of Autoimmunity Available online:8 January 2024
DOI:https://doi.org/10.1016/j.jaut.2023.103165
Abstract
Objective
To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE).
Methods
Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers.
Results
Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE).
Conclusion
In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.
