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Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology.

ABSTRACT: BACKGROUND:Lupus 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. METHODS:In 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. RESULTS:Urinary ALCAM levels were significantly increased in active LN patients when compared to active SLE patients without renal involvement (p?

SUBMITTER: Ding H

PROVIDER: S-EPMC7251704 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology.

Ding Huihua H Lin Cheng C Cai Jingyi J Guo Qiang Q Dai Min M Mohan Chandra C Shen Nan N

Arthritis research & therapy 20200527 1

<h4>Background</h4>Lupus 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.<h4>Methods</h4>In 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.<h4>Results</h4>Urinary ALCAM levels were significantly increased i ...[more]

PMID: 32460901

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Project description:Multiple sclerosis is a chronic neuroinflammatory disorder characterized by demyelination, oligodendrocyte damage/loss and neuroaxonal injury in the context of immune cell infiltration in the central nervous system. No neuroprotective therapy is available to promote the survival of oligodendrocytes and protect their myelin processes in immune-mediated demyelinating diseases. Pro-inflammatory CD4 T helper (Th)17 cells can directly interact with oligodendrocytes in multiple sclerosis and its animal model, causing injury to myelinating processes and cell death through direct contact. However, the molecular mechanisms underlying the close contact and subsequent detrimental interaction of Th17 cells with oligodendrocytes remain unclear. In this study we conducted single cell RNA sequencing of human primary oligodendrocytes cultured alone, in contact or separated by an insert with primary Th17 polarized T cells and identified several cell adhesion molecules that may modulate T cell contact mediated damage of oligodendrocytes. Furthermore, we used flow cytometry and immunofluorescence studies on central nervous system tissue from multiple sclerosis subjects, its animal model and controls to characterize the expression of cell adhesion molecules by mature oligodendrocytes. We found that a significant proportion of human and murine mature oligodendrocytes express melanoma cell adhesion molecule and activated leukocyte cell adhesion molecule in multiple sclerosis, EAE and controls although their regulation differ between human and mouse. We observed that exposure to pro-inflammatory cytokines or to human activated T cells are associated with a marked downregulation of the expression of melanoma cell adhesion molecule but not activated leukocyte cell adhesion molecule at the surface of human primary oligodendrocytes. Furthermore, we used in vitro live-imaging, immunofluorescence, and flow cytometry to determine the contribution of these molecules to Th17-polarized cell adhesion and cytotoxicity towards human oligodendrocytes. Silencing and blocking activated leukocyte cell adhesion molecule but not melanoma cell adhesion molecule limited prolonged interactions between oligodendrocytes and Th17-polarized cells, resulting in decreased adhesion of Th17-polarized cells to oligodendrocytes and conferred significant protection of oligodendrocytic processes.

Dataset Information

Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology.

Publications

Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology.

Similar Datasets

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