LRG1, a novel serum biomarker for iMCD disease activity
Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systematic inflammatory symptoms and multiorgan dysfunction caused by a cytokine storm. The current assessment of treatment response in iMCD lack sensitivity due to the heterogeneity of...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
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| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-025-00767-1 |
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| Summary: | Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systematic inflammatory symptoms and multiorgan dysfunction caused by a cytokine storm. The current assessment of treatment response in iMCD lack sensitivity due to the heterogeneity of clinical features. We performed proteomic analysis using Data Independent Acquisition (DIA) mass spectrometry (MS) on 33 serum samples in different disease states from 17 patients. Leucine-rich alpha-2-glycoprotein-1 (LRG1) emerged as one of the proteins with most significantly different expression, exhibiting lower levels in response to treatment. Enzyme-linked immunosorbent assay (ELISA) on a larger cohort of 146 serum samples (96 disease flare, 28 biochemical partial response, 22 biochemical complete response) from 100 iMCD patients further confirmed this association, demonstrating a significant decrease in serum LRG1 level following successful treatment. Notably, LRG1 remained elevated in patients with ongoing inflammation during siltuximab therapy when CRP failed to accurately reflect disease activity. Additionally, serum CRP/LRG1 ratio differed across iMCD subtypes, suggesting potential variations in inflammatory pathways. These findings support serum LRG1 as a valuable biomarker for iMCD disease treatment response and activity, and may provide insights into underlying disease mechanisms. |
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| ISSN: | 2050-7771 |