THU0249\u2005URINARY NEUTROPHIL GELATINASE ASSOCIATED LIPOCALCIN AND PROSTAGLANDIN D-SYNTHETASE PREDICT DISEASE FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

Background Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease commonly characterized by periods of flares and quiescence. Conventional markers of disease activity (serum complement and anti-dsDNA antibodies) have a limited predictive value of disease flares. Recent evidence suggests that urine biomarkers are able to discriminate between SLE patients with ongoing renal activity and those without nephritis (1-2). Objectives To investigate if urinary Neutrophil Gelatinase Associated Lipocalcin (NGAL) and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS) are early biomarkers that could be used as flare predictors in SLE. Methods Patients prospectively followed at our clinic from March 2017 to September 2018, who fulfilled classification criteria for SLE (3), were considered for the study. Flares were identified by SELENA-SLEDAI Flare Index (SFI) after 3 months of urine collection (4). NGAL and L-PGDS levels were measured in the second void urinary sample by ELISA. Data were compared by the unpaired student’s t test or the Mann–Whitney U test as appropriate. Logistic regression analysis was used to assess the independent baseline predictors of flares. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) with associated 95% confidence interval (CI) to find the best cut-off values. Results Urine specimen was collected from 66 patients, including 64 females and 2 males with a median age at diagnosis of 27 years (IQR 21,5-38). During 3 months-follow-up, 18 (27%) out of the 66 patients experienced a single disease flare. Urinary levels of L-PGDS (Fig. 1) and NGAL (Fig. 2) significantly increased 12 weeks before a disease flare (p=0.0001 and p=0.002, respectively). Urinary NGAL levels correlated with anti-DNA antibody titre (r=0.254, p=0.042) and not with serum complement prior to the disease flare (P>0.05). Moreover, urinary L-PGDS slightly correlated with anti-DNA antibody titre (p=0.08), and was not associated with serum complement levels. Based on ROC analysis, urinary NGAL (AUC: 0.752) and L-PGDS (AUC: 0.811), outperformed conventional biomarkers (Table1). ROC analysis revealed that NGAL levels above 10.95ng/ml had a sensitivity of 84% and a specificity of 63% for flare prediction, while urine L-PGDS cut-off value in the ROC curve, 1500 ng/ml, predicted a flare with 78% sensitivity and 86% specificity. At multivariate analysis, NGAL and L-PGDS were independent predictors of flare with OR=10.34 (95% CI 1.46 – 73.05) and 24.85 (95% CI 4.32-142.68), respectively. Increase in anti-dsDNA antibodies levels also predicted flares with an OR of 6.70 (p=0.040), while hypocomplementemia was not a significant risk factor. Conclusion Urine NGAL and L-PGDS perform better than conventional markers in predicting a lupus flare in its incipient phase, in particular preceding the corresponding change in serum complement. Urinary NGAL and L-PGDS levels seem to be potential tools for monitoring patients with SLE. Further studies are needed to determine their clinical utility in everyday practice. References [1] Rubinstein T, et al. Rheumatol Oxf Engl. 2010;49:960–71. [2] Gupta R, et al. Clin Exp Rheumatol. 2015;33:694-8. [3] Tan EM, et al. Arthritis Rheum. 1982;25:1271–7. [4] Petri M, et al. NEJM2005;353: 2550-58.Table 1 Area under the curve (AUC), cut off values, sensitivity and specificity for L-PGDS, NGAL and standard biomarkers for disease flares. Variables AUC 95% CI Cut off values sensitivity specificity C3 0.683 0.555 - 0.793 107 mg/dl 94% 40% Anti dsDNA antibodies 0.705 0.579 - 0.812 30 UI 55% 89% PGDS 0.811 0.694 - 0.897 1500 ng/ml 78% 86% NGAL 0.752 0.630 - 0.851 10.95 ng/ml 84% 63%Abstract THU0249 – Figure 1Abstract THU0249 – Figure 2 Disclosure of Interests Serena Fasano: None declared, Luciana Pierro: None declared, Alessia Borgia: None declared, Melania Alessia Coscia: None declared, Ranieri Formica: None declared, Antonella Riccardi: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN