Abstract
BackgroundLupus nephritis (LN) is one of the most severe complications of SLE patients. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort.MethodsIn this cross-sectional study, a total of 256 patients and controls were recruited. Urinary levels of ALCAM were determined by ELISA. Renal histopathology was reviewed by an experienced renal pathologist.ResultsUrinary ALCAM levels were significantly increased in active LN patients when compared to active SLE patients without renal involvement (p < 0.001), inactive LN patients (p = 0.023), inactive SLE patients without renal involvement (p < 0.001), and healthy controls (p < 0.001). Correlation analysis revealed a positive correlation between urinary ALCAM and general disease activity—SLEDAI score (r = 0.487, p < 0.001), as well as renal disease activity—rSLEDAI (r = 0.552, p < 0.001) and SLICC RAS (r = 0.584, p < 0.001). Urinary ALCAM also correlated with lab parameters including 24-h urine protein, hemoglobin, and complement 3. Moreover, urinary ALCAM levels were significantly increased in class III and IV (proliferative) LN as compared to those in class V (membranous) LN. It outperformed conventional biomarkers (anti-dsDNA antibody, C3, C4, proteinuria) in discriminating the two groups of LN. On renal histopathology, urinary ALCAM levels correlated positively with activity index (r = 0.405, p < 0.001) but not chronicity index (r = 0.079, p = 0.448).ConclusionUrinary ALCAM is a potential biomarker for predicting renal pathology activity in LN and may serve as a valuable surrogate marker of renal histopathology.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease that has a wide impact on multiple organs, including the kidneys
Urinary ALCAM is a potential biomarker for predicting renal pathology activity in Lupus nephritis (LN) and may serve as a valuable surrogate marker of renal histopathology
Elevated urinary ALCAM in active lupus nephritis patients. In this cross-sectional study, urinary ALCAM levels were significantly increased in active LN patients (11.50 Interquartile range (IQR) (16.79) ng/mg) when compared to active SLE patients without renal involvement (3.51 IQR (6.20) ng/mg, p < 0.001), inactive LN patients (3.46 IQR (5.14) ng/mg, p = 0.023), inactive SLE patients without renal involvement (2.45 IQR (4.04) ng/mg, p < 0.001), and healthy controls (1.79 IQR (1.23) ng/mg, p < 0.001) (Fig. 1a)
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease that has a wide impact on multiple organs, including the kidneys. Our preliminary aptamer-based proteomic screening study identified several novel urinary biomarkers for active LN [6]. Among these proteins, activated leukocyte cell adhesion molecule (ALCAM or CD166) turned out to be a promising biomarker for LN. Soluble ALCAM in body fluids is produced through proteolytic cleavage by ADAM17 or alternative splicing [8, 9] It plays an important role in T cell activation and immune cell adhesion and migration through its interaction with CD6 [10, 11]. We aim to further validate the performance of urinary ALCAM as a biomarker in assessing disease activity and renal histopathology in a Chinese LN cohort. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort
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