{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:49Z","timestamp":1792553389768,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Mechanisms contributing to non\u2010response to treatment in lupus nephritis (LN) are unclear. We characterised the transcriptome of paired peripheral blood mononuclear cells (PBMCs) and renal tissues in LN before and after cyclophosphamide (CYC) treatment and identified markers that predicted treatment response. Total RNA isolated from paired PBMCs (<jats:italic>n<\/jats:italic>\u2009=\u200932) and renal tissues (<jats:italic>n<\/jats:italic>\u2009=\u200925) of 16 proliferative LN before CYC treatment, 6\u2009months post\u2010treatment, and during renal flare, was sequenced on Illumina Novaseq\u20106000 platform. Post\u2010treatment, eight patients were clinical responders (CR), of whom four flared (FL), and eight were non\u2010responders (NR). Comparative transcriptomic analyses before and after treatment within CR, NR, and FL groups was performed using DESeq2. Weighted gene co\u2010expression network analysis (WGCNA) and ROC analysis was performed to identify and validate hub genes predictive of treatment response. Based on this, we observed that pathways such as degradation of cell cycle proteins, expression of G0 and G1 phase proteins, and apoptosis, were upregulated in CR PBMCs post\u2010treatment, while IFN\u2010\u03b3 signalling and ECM organisation were downregulated. In NR PBMCs, ECM molecules, neddylation and BCR signalling were upregulated post\u2010CYC treatment, while in NR renal tissue, TLR, IFN and NF\u2010\u03baB signalling pathways were upregulated. In FL PBMCs, neutrophil degranulation and ROS and RNS production in phagocytes were downregulated following treatment, whereas, in the corresponding renal tissue, cell\u2010ECM interactions and <jats:italic>ISG15<\/jats:italic> antiviral mechanism were downregulated. After WGCNA and subsequent ROC analysis, <jats:italic>TENM2, NLGN1<\/jats:italic> and <jats:italic>AP005230.1<\/jats:italic> from PBMCs each predicted NR (AUC\u20100.91; <jats:italic>p<\/jats:italic>\u2009=\u20090.03), while combined model improved prediction (AUC\u20100.94; <jats:italic>p<\/jats:italic>\u2009=\u20090.02). <jats:italic>AP005230.1<\/jats:italic> from renal tissue also predicted non\u2010response (AUC\u20100.94; <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and <jats:italic>AC092436.3<\/jats:italic> from PBMCs predicted renal flare (AUC\u20100.81; <jats:italic>p<\/jats:italic>\u2009=\u20090.04). Our study identified significant DEGs\/pathways specific to different treatment outcomes and hub genes that predicted non\u2010response and renal flare.<\/jats:p>","DOI":"10.1111\/imm.13891","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T02:54:37Z","timestamp":1738119277000},"page":"470-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus Nephritis\u2014A Prospective Study"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-0479","authenticated-orcid":false,"given":"Sree Nethra","family":"Bulusu","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Post\u2010Graduate Medical Education and Research (JIPMER)  Puducherry 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 Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Mary","family":"Mariaselvam","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Post\u2010Graduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengappa","family":"Kavadichanda","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Jawaharlal Institute of Post\u2010Graduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi Sridhar","family":"Vembar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology (IBAB)  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly Mary","family":"Thabah","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology 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