Leucine-rich alpha-2-glycoprotein 1 (LRG1) decrement during biologics therapy and its correlation with disease features and treatment outcomes in rheumatoid arthritis patients

Abstract

Objectives: Leucine-rich alpha-2-glycoprotein 1 (LRG1) was previously reported to regulate inflammation and arthritis progression. This study aimed to investigate the correlation of serum LRG1 level with disease features and response to biologics in rheumatoid arthritis (RA) patients.

Methods: Seventy-eight RA patients who underwent biologics treatment were analyzed. Serum LRG1 level was detected by enzyme-linked immunosorbent assay at baseline (before biologics were initiated) and at weeks 6 and 12. Treatment response, low disease activity (LDA), and remission were analyzed on the basis of disease activity score in 28 joints. Moreover, serum LRG1 level in another 20 health controls was also analyzed.

Results: LRG1 was greater in RA patients than in health controls (46.3 versus 28.6 µg/mL, P < 0.001), with an area under the curve of 0.795 for differentiating them according to the receiver operator characteristic curve. By correlation analysis, LRG1 was correlated with a greater body mass index (P = 0.007) and C-reactive protein level (P = 0.013) in RA patients and tended to be associated with swollen joint count but was not statistically significant (P = 0.052). Furthermore, LRG1 decreased from baseline to week 12 after biologics treatment in RA patients (P < 0.001). However, baseline LRG1 was not correlated with treatment response (P = 0.987), LDA (P = 0.405), or remission (P = 0.763) in RA patients. A decrease in LRG1 at week 12 (P = 0.028) was related to response achievement, and a decrease in LRG1 at week 6 (P = 0.047) and week 12 (P = 0.019) was related to LDA achievement.

Conclusion: LRG1 may aid in RA disease supervision, but further validation is needed. Key Points • LRG1 level can distinguish RA patients from health controls with a high AUC at 0.795. • LRG1 level is correlated with higher BMI and CRP level, and tends to be related to elevated SJC in RA patients. • LRG1 level after treatment is correlated with clinical response and LDA to biologics in RA patients, while its level before treatment fails to do so. • Collectively, LRG1 level shows a potential to be a biomarker for RA disease supervision.

Keywords: Disease activity; Health controls; Response to biologics; Rheumatoid arthritis; Serum LRG1.

Fig. 1

Dysregulated LRG1 level. Comparison of LRG1 level between RA patients and health controls (A). ROC curve analysis of LRG1 level for distinguishing RA patients from health controls (B). Diagnostic indexes of LRG1 level by different cutoffs for RA (C)

Fig. 2

Treatment outcomes at different timepoints. DAS28_ESR score at baseline, week 6, and week 12 (A). Response rate at baseline, week 6, and week 12 (B). LDA rate at baseline, week 6, and week 12 (C). Remission rate at baseline, week 6, and week 12 (D)

Fig. 3

LRG1 decrement related to treatment outcome to some extent. LRG1 level at baseline, week 6, and week 12 (A). Comparison of LRG1 level at baseline, week 6, and week 12, between response RA patients and no response RA patients (B), between LDA RA patients and no LDA RA patients (C), between remission RA patients and no remission RA patients (D)