Abstract
Objective: To investigate the relationship between serum Leucine-Rich α-2-Glycoprotein-1 (LRG1) and idiopathic multicentric Castleman disease (iMCD) activity, and to verify the effectiveness of LRG1 in monitoring treatment response.
Methods: Clinical data and serum samples were collected from iMCD patients in flare and remission state diagnosed between August 2015 and April 2022 in Peking Union Medical College Hospital. Enzyme-linked Immunosorbent Assay was performed to quantify LRG1 concentration, which was further analyzed with patients' clinical data.
Results: 81 patients were included, with 10 cases of iMCD-TAFRO and 40 cases of severe-disease, and 110 serum samples were acquired. The average LRG1 concentration was 113.5±14.27μg/mL in 76 samples of disease flare, 47.48±14.23μg/mL in 16 biochemical PR, and 14.4±1.18μg/mL in 18 biochemical CR samples. The difference is significant among different disease states (Flare vs PR, p = 0.0019; Flare vs CR, p < 0.0001; PR vs CR, p = 0.0349). Paired sample of 20 cases showed significant decrease of serum LRG1 from Flare to PR/CR (-35.36±5.94μg/mL, p < 0.0001) after treatment (figure 1A). Serum LRG1 level was also elevated in those iMCD-TAFRO cases with normal serum CRP level during disease flare. Baseline LRG1 level was significantly higher in patients with severe disease (142.6±23.2μg/mL vs 81.2±14.0μg/mL, p = 0.0271), which could be identified efficiently by baseline LRG1 over 57.75μg/mL (AUC = 0.655, p = 0.0203, sensitivity 70%, specificity 63.89%). Among 38 patients using thalidomide-cyclophosphamide-prednisone (TCP) regimen as first-line treatment, the median time to next treatment in patients with baseline LRG1 over 57.75μg/mL was significantly shorter than those under 57.75μg/mL (10 vs 30 months, HR: 2.254, 95% CI: 1.052-4.828, p = 0.0277) (figure 1B).
Conclusion: Serum LRG1 level could mirror disease activity, and could be utilized to monitor the treatment response, especially in iMCD-TAFRO subtype. Serum LRG1 level over 57.75μg/mL could efficiently identify patients with severe iMCD, and had the potential to predict the efficacy of TCP regimen.
Disclosures
No relevant conflicts of interest to declare.
