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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-025-00767-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849726428546859008 |
|---|---|
| author | Miao-yan Zhang Zi-han Yang Yu-chong Qiu Yu-han Gao Si-yuan Li Yue Dang Lu Zhang Jian Li |
| author_facet | Miao-yan Zhang Zi-han Yang Yu-chong Qiu Yu-han Gao Si-yuan Li Yue Dang Lu Zhang Jian Li |
| author_sort | Miao-yan Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e2ece620fad743d9844c1966318e6b82 |
| institution | DOAJ |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-e2ece620fad743d9844c1966318e6b822025-08-20T03:10:10ZengBMCBiomarker Research2050-77712025-04-011311510.1186/s40364-025-00767-1LRG1, a novel serum biomarker for iMCD disease activityMiao-yan Zhang0Zi-han Yang1Yu-chong Qiu2Yu-han Gao3Si-yuan Li4Yue Dang5Lu Zhang6Jian Li7Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract 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.https://doi.org/10.1186/s40364-025-00767-1Leucine-rich alpha-2-glycoprotein-1 (LRG1)Idiopathic Multicentric Castleman Disease (iMCD)BiomarkerProteomics |
| spellingShingle | Miao-yan Zhang Zi-han Yang Yu-chong Qiu Yu-han Gao Si-yuan Li Yue Dang Lu Zhang Jian Li LRG1, a novel serum biomarker for iMCD disease activity Biomarker Research Leucine-rich alpha-2-glycoprotein-1 (LRG1) Idiopathic Multicentric Castleman Disease (iMCD) Biomarker Proteomics |
| title | LRG1, a novel serum biomarker for iMCD disease activity |
| title_full | LRG1, a novel serum biomarker for iMCD disease activity |
| title_fullStr | LRG1, a novel serum biomarker for iMCD disease activity |
| title_full_unstemmed | LRG1, a novel serum biomarker for iMCD disease activity |
| title_short | LRG1, a novel serum biomarker for iMCD disease activity |
| title_sort | lrg1 a novel serum biomarker for imcd disease activity |
| topic | Leucine-rich alpha-2-glycoprotein-1 (LRG1) Idiopathic Multicentric Castleman Disease (iMCD) Biomarker Proteomics |
| url | https://doi.org/10.1186/s40364-025-00767-1 |
| work_keys_str_mv | AT miaoyanzhang lrg1anovelserumbiomarkerforimcddiseaseactivity AT zihanyang lrg1anovelserumbiomarkerforimcddiseaseactivity AT yuchongqiu lrg1anovelserumbiomarkerforimcddiseaseactivity AT yuhangao lrg1anovelserumbiomarkerforimcddiseaseactivity AT siyuanli lrg1anovelserumbiomarkerforimcddiseaseactivity AT yuedang lrg1anovelserumbiomarkerforimcddiseaseactivity AT luzhang lrg1anovelserumbiomarkerforimcddiseaseactivity AT jianli lrg1anovelserumbiomarkerforimcddiseaseactivity |