Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity
Objective Proteomic 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.Methods This study recruited 10 patients with proliferative LN and 6 normal...
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BMJ Publishing Group
2021-04-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/8/1/e000569.full |
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| author | Minghui Zhao Ying Tan Feng Yu Zhaomin Mao |
| author_facet | Minghui Zhao Ying Tan Feng Yu Zhaomin Mao |
| author_sort | Minghui Zhao |
| collection | DOAJ |
| description | Objective Proteomic 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.Methods This 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).Results Proteomics 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).Conclusions Renal NEU1 expression was associated with pathological CI scores and renal outcomes in patients with proliferative LN. |
| format | Article |
| id | doaj-art-5d6bcabb9f9b4edc8f6f8506209759ae |
| institution | OA Journals |
| issn | 2053-8790 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | BMJ Publishing Group |
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| series | Lupus Science and Medicine |
| spelling | doaj-art-5d6bcabb9f9b4edc8f6f8506209759ae2025-08-20T02:36:23ZengBMJ Publishing GroupLupus Science and Medicine2053-87902021-04-018110.1136/lupus-2021-000569Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicityMinghui Zhao0Ying Tan1Feng Yu2Zhaomin Mao3Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, People`s Republic of ChinaITaMed Ltd., Shanghai, China1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Beijing, People`s Republic of ChinaObjective Proteomic 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.Methods This 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).Results Proteomics 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).Conclusions Renal NEU1 expression was associated with pathological CI scores and renal outcomes in patients with proliferative LN.https://lupus.bmj.com/content/8/1/e000569.full |
| spellingShingle | Minghui Zhao Ying Tan Feng Yu Zhaomin Mao Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity Lupus Science and Medicine |
| title | Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| title_full | Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| title_fullStr | Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| title_full_unstemmed | Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| title_short | Discovery of NEU1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| title_sort | discovery of neu1 as a candidate renal biomarker for proliferative lupus nephritis chronicity |
| url | https://lupus.bmj.com/content/8/1/e000569.full |
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