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ArticleClinical rheumatology2025

Combined transcriptomics and proteomics analysis reveals mechanisms underlying refractory lupus nephritis in children.

Qijiao Wei, Yifan Li, Haimei Liu, Wanzhen Guan, Yinv Gong, Qiaoqian Zeng, Qianying Lv, Xiaomei Zhang, Ling Yang, Hong Xu and 1 more

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Article in Clinical rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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11 authors.

Qijiao Wei *Department of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.ORCID http://orcid.org/0000-0002-7791-0630
Yifan Li *Department of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Haimei LiuDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Wanzhen GuanDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Yinv GongDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Qiaoqian ZengDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Qianying LvDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Xiaomei ZhangDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Ling YangDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Hong XuDepartment of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China. hxu@shmu.edu.cn.
Li SunDepartment of Rheumatology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China. lillysun@263.net.

Funding

Shanghai Pujiang Young Rheumatologists Training Program SPROG2403
6 · The paper itself

Abstract

backgroundsLupus nephritis (LN) is a major cause of morbidity among patients with systemic lupus erythematosus (SLE). Unfortunately, some patients do not respond adequately to available therapies, and the gene expression changes underlying this refractory state are still poorly understood. Therefore, it is crucial to gain a better understanding of the molecular mechanisms involved in refractory LN.

methodsIntegrated proteomic and transcriptomic analysis was conducted to characterize the unique gene expression profiles in patients with refractory LN. DEGs/DAPs were identified based on the concordance between transcriptome and proteome data. Subsequently, functional enrichment analyses and protein-protein interaction network analyses were performed. Module analysis was carried out using the Search Tool for the Retrieval of Interacting Genes and Cytoscape software. Additionally, the clinical features of these patients were explored. To identify potential therapeutic agents, the Connectivity Map L1000 platform was employed.

resultsSeventeen patients were included in the study, 12 non-refractory LN and 5 refractory LN. There was no statistically significant difference in demographic data, clinical characteristics and laboratory findings. There were 1019 DAPs in non-refractory LN compared with refractory LN and 47 DEGs totally in glomeruli and tubulointerstitium from GSE200306 dataset between two groups. Finally, we obtained 7 DEGs/DAPs, including CD59, JAK1, VCAM1, C8A, PIGR, TGFBI and VTN. The functions and pathways associated with the DEGs/DAPs mainly associated with complement and coagulation cascades. We also found that T cells CD4 memory (activated) downregulated in refractory LN. In both proteomics and transcriptomics analysis, CD59 was downregulated in refractory LN. And CD59 positively correlated with Alb and negatively correlated with CH50. In addition, we discovered several chemicals as potential treatment options for refractory LN.

conclusionsAccording to our research findings, we have discovered that abnormal activation and functional defects of the complement system play a significant role in refractory lupus nephritis. In particular, the decreased expression of CD59 indicates abnormal complement activation. Therefore, inhibiting complement activation may become a new strategy for treating refractory LN. Key Points • The first explore of specific gene expression changes associated with refractory LN combined transcriptomics and proteomics analysis. • The functions and pathways associated with the DEGs/DAPs mainly associated with complement and coagulation cascades. • CD59 was downregulated in refractory LN. CD59 positively correlated with Alb and negatively correlated with CH50.

Indexed as

Lupus NephritisTranscriptomeAdolescentChildFemaleGene Expression ProfilingHumansMaleProtein Interaction MapsProteomeProteomicsProteomeComplement activationProteomicsRefractory lupus nephritisSystemic lupus erythematosusTranscriptomics

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.