Exploration of Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) and Its Association with Proangiogenic Mediators in Sickle Cell Disease: A Potential Player in the Pathogenesis of the Disease.

OBJECTIVE

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a novel mediator involved in abnormal angiogenesis. We aimed to investigate circulating LRG1 levels and their relationship with proangiogenic mediators in sickle cell disease (SCD).

MATERIALS AND

METHODS

A total of 50 patients with SCD, with 25 in steady-state condition (SCD-SS) and 25 in periods of painful vaso-occlusive crisis (SCD-VOC), and 25 healthy controls were included in the study. Demographical and clinical data were collected from hospital records. Serum LRG1, vascular endothelial growth factor A (VEGFA), and hypoxia-inducible factor 1-alpha (HIF1A) levels were measured by enzyme-linked immunosorbent assay (ELISA), and C-reactive protein (CRP) was measured by the nephelometric method. Routine biochemical parameters were assessed using an autoanalyzer. Multinomial logistic regression was used to analyze ELISA parameters, and receiver operating characteristic (ROC) curves were constructed to determine the optimal cut-off point for HIF1A to predict VOCs in SCD patients.

RESULTS

LRG1 and VEGFA levels were significantly higher in SCD patients than controls (p<0.001), with no difference between the SCD-SS and SCD-VOC groups. HIF1A, CRP, and lactate dehydrogenase levels differed significantly across all groups, being highest in the SCD-VOC group (p<0.001). After adjusting for age and sex, LRG1, HIF1A, and VEGFA remained elevated in the SCD groups. HIF1A correlated with CRP (r=0.351, p=0.024), but LRG1 showed no correlation with proangiogenic mediators in the SCD-VOC group. The area under the ROC curve was calculated as 0.694 (95% confidence interval: 0.542-0.845, p=0.021) and the optimal cut-off point was 494.5 pg/mL for HIF1A in predicting vaso-occlusive crises in patients with SCD.

CONCLUSION

Circulating LRG1 levels may reflect neutrophil activation and contribute to the cross-talk between proangiogenic mediators released in SCD.