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Background: In systemic lupus erythematosus (SLE), disease activity is comprehensively evaluated based on general, organ-specific, and serological indices, and systemic lupus erythematosus disease activity index (SLEDAI)-2K score is used; however, SLEDAI-2K score consists of 24 evaluation items, making evaluation complicated and costly to evaluate all of them in daily clinical practice, there is a need to develop new serum markers that better reflect disease activity. Leucine-rich α2-glycoprotein (LRG) is an inflammatory protein identified in our laboratory and is currently in practical use as a marker of activity in inflammatory bowel disease [1, 2]. LRG production is induced not only by IL-6 but also by various cytokines such as TNF-α and IL-1β. Therefore, LRG may be useful in detecting disease activity in SLE, which is known as an IL-6-independent inflammatory disease.
Objectives: The aim of this study was to investigate the usefulness of LRG as a novel biomarker for disease activity in SLE, which has characteristics that differ from those of existing autoantibodies, complement, and CRP.
Methods: Patients were selected from SLE patients who visited our department between April 2021 and September 2024. SLEDAI-2K score and serum level of anti-ds-DNA antibodies, C3, C4, CRP, and LRG were measured before therapeutic intervention and 6 months after therapeutic intervention. Clinical and laboratory data were collected from medical records and three statistical analyses were conducted. First, the correlation between serum level of LRG and each activity marker was analyzed. Then, we extracted the patients with low serum level of CRP (<0.14 mg/dl) before treatment from these patients. The correlation between serum level of LRG and SLEDAI-2K score was analyzed. Second, changes in each activity marker before and after treatment were analyzed. Third, we defined low disease activity of SLE as SLEDAI-2K ≤4 [3], and divided the patients into two groups: low disease activity group (SLEDAI-2K ≤4) and high disease activity group (SLEDAI-2K ≥5). Then, the ROC curve was used to compare the discriminatory ability of each activity marker between low and high disease activity group.
Results: Ninety-six patients were enrolled. 77% were women and mean age at inclusion was 44.2 ± 16.6 years old. Mean SLEDAI-2K score was 11.8 ± 8.54. Serum level of LRG correlated with SLEDAI-2K score and serum level of anti-ds-DNA antibody and CRP (r=0.29, 0.24 and 0.82 respectively), but not with serum level of C3 and C4 (r=-0.063 and -0.067). Then, in patients with low titer of CRP (<0.14 mg/dl) before treatment (n=19), serum level of LRG was correlated with SLEDAI-2K score and serum level of anti-ds-DNA antibody, C3, C4, and CRP (r=0.65, 0.50, -0.21, -0.32, and 0.43 respectively). After treatment, serum level of LRG was significantly decreased (P<0.001), and SLEDAI-2K score and serum level of anti-ds-DNA antibody, C3, C4, and CRP were also significantly improved (P=0.0044, 0.0018, 0.027, 0.0022, and <0.001 respectively). When ROC curve analysis was conducted to compare the discriminatory ability of each activity marker between low and high disease activity group (n=37 and 59), the AUC of serum level of LRG was 0.718, which was equivalent to activity markers such as serum level of anti-ds-DNA antibody, C3, C4, and CRP (0.680, 0.635, 0.608, and 0.697 respectively).
Conclusion: Serum LRG may detect disease activity in SLE that is difficult to detect with CRP, and may be a novel biomarker of disease activity.
REFERENCES: [1] Inflamm Bowel Dis. 2012; 18(11):2169-79
[2] J Crohns Colitis. 2017 Jan;11(1):84-91
[3] Lancet Rheumatol. 2019; 1(2)e95-e102.
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (