Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity

Abstract

ObjectiveProteomic approach was applied to identify candidate biomarkers of chronicity in patients with proliferative lupus nephritis (LN), and their clinicopathological significance and prognostic values were investigated.MethodsThis study recruited 10 patients with proliferative LN and 6 normal controls (NCs) with proteomic data to compare protein expression profiles, 58 patients with proliferative LN and 10 NCs to verify proteomic data by immunohistochemistry, and 14 patients with proliferative LN with urine samples to evaluate the urinary expression of the biomarker by western blot assay. The composite endpoints included end-stage renal disease and ≥50% reduction from baseline estimated glomerular filtration rate (eGFR).ResultsProteomics detected 48 proteins upregulated in the group with chronicity index (CI) ≥1 compared with the CI=0 and NC groups. Further pathway analysis was enriched in ‘other glycan degradation’. Neuraminidase 1 (NEU1), the most predominant protein in the pathway of other glycan degradation, was highly expressed in the kidney of patients with proliferative LN and could co-localise with podocyte, mesangial cells, endothelial cells and tubule cells. NEU1 expression in the tubulointerstitium area was significantly higher in the CI ≥1 group compared with the CI=0 and NC groups. Moreover, NEU1 expression was significantly correlated with serum creatinine value, eGFR and CI scores, respectively. Urinary NEU1 excretion in the CI ≥1 group was higher than in the CI=0 group and was also positively correlated with CI scores. Furthermore, the high expression of renal NEU1 was identified as an independent risk factor for renal prognosis by multivariate Cox regression analysis (HR, 6.462 (95% CI 1.025 to 40.732), p=0.047).ConclusionsRenal NEU1 expression was associated with pathological CI scores and renal outcomes in patients with proliferative LN.

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

“…Pathways include metabolism [55], neutrophil degranulation [56], metabolism of lipids [57], immune system [58], metabolism of proteins [59] and TP53 [60] regulates metabolic genes were linked with progression of T1DM. KDM7A [61], LMNA (lamin A/C) [62], PFKFB3 [63], NEU1 [64], DUSP22 [65], ADORA2B [66], CRTC2 [67], GRN (granulin precursor) [68], CTSD (cathepsin D) [69], IGFBP4 [70], SMYD2 [71], OSM (oncostatin M) [72], INVS (inversin) [73], ANKFY1 [74], SEMA4D [75], PPM1A [76], IFNG (interferon gamma) [77], CTBP1 [78], ATP6 [79], COX2 [80], RPS19 [81], COX1 [82] and TLK1 [83] are potential biomarkers for the detection and prognosis of renal diseases. A previous study reported that LXN (latexin) [84], LMNA (lamin A/C) [85], PFKFB3 [86], NEU1 [87], TBK1 [88], GRN (granulin precursor) [89], CTSD (cathepsin D) [90], ACADS (acyl-CoA dehydrogenase short chain) [91], IRF7 [92], S1PR1 [93], ZAP70 [94], IDH1 [95], IL15 [96], PIK3R1 [97], OSM (oncostatin M) [98], SOCS3 [99], USP21 [100], CEP19 [101], KDM2A [102], TP53 [103], BRD2 [104], ATP6 [105], BRD4 [106], COX2 [107], RPS6 [108], ND2 [109], CYTB (cytochrome b) [110] and COX1 [111] are altered expressed in obesity.…”

Podocyte injury and death: New insights into lupus nephritis pathogenesis and therapy

“…These components are, therefore, potential biomarkers for LN diagnosis and monitoring (Table 2). [41][42][43][44][45][46][47] For example, variations in urinary sediment podocin and podocalyxin levels among LN patients emphasize the diagnostic value of podocyte components. 41…”

“…Urinary sediment podocin (used Pod) mRNA Associated with severe proliferative LN [41] Urinary supernatant podocalyxin protein Associated with subepithelial dense deposit LN Neuraminidase 1 Associated with pathological CI scores and renal outcomes in patients with proliferative LN [42] Podocyte-derived microparticles Positively correlated with increased proteinuria [43] Cmaf-inducing protein Be limited to nonproliferative forms and may define a specific pattern of podocyte injury in LN [44] Podocalyxin Urinary podocalyxin level significantly predicts the pathological impact of SLE on the kidney [45] Soluble urokinase plasminogen activator receptor Urine suPAR levels raised again in patients with a relapse of LN [46] S100 proteins Higher urine S100 levels are associated with increased LN activity in childhood-onset SLE [47] Abbreviations: CI, chronicity index; LN, lupus nephritis; mRNA, messenger RNA; SLE, systemic lupus erythematosus, suPAR, soluble urokinase plasminogen activator receptor. phosphorylation of nephrin in LN.…”

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

“…In human studies, proteomic analysis of renal tissues comparing patients with proliferative lupus nephritis vs . healthy controls revealed NEU1 as the greatest up-regulated protein of 48 identified proteins ( 341 ). NEU1 immunohistochemical staining and urinary excretion were significantly elevated in lupus nephritis patients compared with controls.…”