# LRG1, a novel serum biomarker for iMCD disease activity

## TL;DR

This study identifies LRG1 as a new blood biomarker for tracking treatment response and disease activity in iMCD, a rare inflammatory lymphoproliferative disorder.

## Contribution

LRG1 is proposed as a novel and sensitive serum biomarker for assessing iMCD disease activity and treatment response.

## Key findings

- Serum LRG1 levels significantly decrease following successful treatment of iMCD.
- LRG1 remains elevated during siltuximab therapy when CRP fails to reflect disease activity.
- CRP/LRG1 ratio varies across iMCD subtypes, indicating potential differences in inflammatory pathways.

## 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.

The online version contains supplementary material available at 10.1186/s40364-025-00767-1.