Session Information
Date: Saturday, November 6, 2021
Title: SLE – Diagnosis, Manifestations, & Outcomes Poster I: Diagnosis (0323–0356)
Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: There remains unmet needs of non-invasive markers of disease activity, damage, prognosis, and treatment response in lupus nephritis patients. Here, we aim to validate urinary L-selectin (CD62L) as a novel biomarker of disease activity and histological changes of LN in a Chinese SLE cohort.
Methods: In a single center Chinese lupus cohort, a total of 197 SLE patients were recruited. 33 chronic kidney disease (CKD) patients and 27 health volunteers were also included as controls. Urine L-selective levels were tested using ELISA. Clinical characteristics and laboratory tests were collected at baseline. Renal histopathology was viewed by an experienced renal pathologist for paired urine-kidney biopsy samples from active LN patients. Furthermore, 18 patients with active LN were followed up for a minimum of 6 months, and we valuated their clinical outcomes and, simultaneously, retested their urine L-selective levels at the end of follow up.
Results: In the cross-sectional cohort, urine L-selectin was significantly increased in active lupus nephritis (aLN) patients (n=89) exclusively compared with active SLE patients without renal involvement (aNR) (n=57) (p < 0.0001), inactive LN patients (iLN) (n=25) (p < 0.0001), inactive SLE patients without renal involvement (n=26) (p < 0.0001), chronic kidney disease (CKD) patients (n=33) (p < 0.0001), and health controls (n=27) (p < 0.0001) (Fig.1A). ROC analysis further confirmed that urine L-selectin had the better capacity to discriminate aLN patients from other groups, especially from aNR patients (Fig.1B), outperforming conventional indices (C3, C4 and anti-dsDNA) (Fig.1C). Correlation analysis exhibited urine L-selectin correlated well with the SLEDAI score (r = 0.491, p < 0.0001), renal SLEDAI (rSLEDAI) score (r = 0.651, p < 0.0001), and SLICC renal activity score (SLICC RAS) (r = 0.526, p < 0.0001) (Fig.1D-1F). Moreover, urine L-selectin positively correlated with activity index (AI) (r = 0.313, p < 0.01) and negatively correlated with chronicity index (CI) (r = -0.308, p < 0.01) of renal pathology. It also strongly correlated with their related pathological attributes (endocapillary hypercellularity, fibrinoid necrosis and/or karyorrhexis, wire loop deposits, interstitial inflammation; glomerulosclerosis, fibrous crescents, interstitial fibrosis and tubular atrophy) (all p < 0.05) (Fig.2A-2C). In the follow-up cohort, 12 patients achieved complete remission or partial remission, while 6 patients still maintained no remission. In remission group, urine L-selectin levels at the end of follow up were lower than those at baseline (p < 0.01) (Fig.3A). While in non-remission group, urine L-selectin levels showed no differences between the baseline and the end of follow up (p = 0.44) (Fig.3B).
Conclusion: Urine L-selectin is a novel biomarker of lupus nephritis disease activity and potential to predict renal histopathology. Besides, it may reflect treatment response of patients in clinical situation.
(A) Urine L-selectin was significantly elevated exclusively in aLN patients when compared with HC (ng/mg), or aNR, iLN, iNR patients, or even CKD patients. (B) Receiver operating characteristic curve analysis (ROC) showed urine L-selectin significantly discriminated aLN patients from aNR, iLN, iNR, CKD and HC. Values in the plot indicate areas under curve. (C) ROC analysis showed urine L-selectin outperformed C3, C4 or anti-dsDNA antibody in discriminating active lupus nephritis (aLN) from active non-renal SLE (aNR). Values in the plot indicate areas under curve (AUC). (D, E, F) Urine L-selectin was correlated significantly with SLEDAI, rSLEDAI and SLICC RAS. aLN, active lupus nephritis; HC, health control; aNR, active non-renal; iLN, inactive lupus nephritis; iNR, inactive non-renal; CKD, chronic kidney disease; C3, complement 3; C4, complement 4; R, Spearman’s correlation coefficient; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; rSLEDAI, renal SLEDAI; SLICC RAS, SLICC renal activity score; ****P<0.0001.
(A) Correlation heatmap analysis for comparison of L-selectin and conventional metrics (C3, anti-dsDNA and 24h Upro) in AI, CI and their component attributes. The size and color of circles reflected the corresponding correlation coefficient values (R) of correlation analysis. The larger the circle, the bigger the value. Circles in which the corresponding R values were over 0.05 were removed off the squares. (B, C) Correlation analysis between urine L-selectin and AI, CI in renal histopathology. AI, activity index; CI, chronicity index; DNA, anti-dsDNA antibody; 24h Upro, 24-hour urine protein quantity; AI_1, Endocapillary hypercellularity; AI_2, Glomerular leukocyte infiltration; AI_3, Cellular and/or fibrocellular crescents; AI_4, Fibrinoid necrosis and/or karyorrhexis; AI-5, Wire loop deposits; AI-6, Interstitial inflammation; CI_1, Glomerulosclerosis; CI_2, Fibrous crescents; CI_3, Interstitial fibrosis; CI_4, Tubular atrophy; R, Spearman’s correlation coefficient; **P<0.01.
The urine L-selectin levels (A) decreased in remission group (CR+PR) (n=12), while (B) remained stable in non-remission group (NR) (n=6). Mann-Whitney U test. N-remission, non-remission. *** P<0.001.
To cite this abstract in AMA style:
Ding H, Shen Y, Dai M, Mohan C, Shen N. Urinary L-selectin Predicts Disease Activity and Histological Changes in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/urinary-l-selectin-predicts-disease-activity-and-histological-changes-in-lupus-nephritis/. Accessed .« Back to ACR Convergence 2021
ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-l-selectin-predicts-disease-activity-and-histological-changes-in-lupus-nephritis/