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

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          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.


          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.


          Urinary 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).


          Urinary ALCAM is a potential biomarker for predicting renal pathology activity in LN and may serve as a valuable surrogate marker of renal histopathology.

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          Most cited references 31

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          The classification of glomerulonephritis in systemic lupus erythematosus revisited.

          The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
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            Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system.

            Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.
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              Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis.

              Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Approximately 40-70% of patients with SLE will develop lupus nephritis. Renal assault during SLE is initiated by genes that breach immune tolerance and promote autoantibody production. These genes might act in concert with other genetic factors that augment innate immune signalling and IFN-I production, which in turn can generate an influx of effector leucocytes, inflammatory mediators and autoantibodies into end organs, such as the kidneys. The presence of cognate antigens in the glomerular matrix, together with intrinsic molecular abnormalities in resident renal cells, might further accentuate disease progression. This Review discusses the genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis. We have categorized the genes identified in human studies of SLE into one of four pathogenic events that lead to lupus nephritis. We selected these categories on the basis of the cell types in which these genes are expressed, and the emerging paradigms of SLE pathogenesis arising from murine models. Deciphering the molecular basis of SLE and/or lupus nephritis in each patient will help physicians to tailor specific therapies.

                Author and article information

                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                27 May 2020
                27 May 2020
                : 22
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, , Shanghai Jiao Tong University School of Medicine, ; 145 Shandong (M) Rd, Shanghai, 200001 China
                [2 ]GRID grid.266436.3, ISNI 0000 0004 1569 9707, Department of Biomedical Engineering, , University of Houston, ; 3517 Cullen Blvd, Room 2027, Houston, TX 77204-5060 USA
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, China-Australia Centre for Personalized Immunology, Renji Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, China
                [4 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, , Shanghai Jiao Tong University School of Medicine (SJTUSM), ; Shanghai, 200032 China
                [5 ]Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, 518040 China
                [6 ]GRID grid.239573.9, ISNI 0000 0000 9025 8099, Center for Autoimmune Genomics and Etiology, , Cincinnati Children’s Hospital Medical Center, ; Cincinnati, OH USA
                [7 ]GRID grid.24827.3b, ISNI 0000 0001 2179 9593, Department of Pediatrics, , University of Cincinnati College of Medicine, ; Cincinnati, OH USA
                © The Author(s) 2020

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                Funded by: FundRef, Innovative Research Group Project of the National Natural Science Foundation of China;
                Award ID: 81421001
                Award Recipient :
                Funded by: FundRef, National Natural Science Foundation of China;
                Award ID: 31630021
                Award ID: 31930037
                Award Recipient :
                Funded by: FundRef, Key Disciplines Construction Project of Shanghai Municipal;
                Award ID: 2017ZZ01024-002
                Award Recipient :
                Research Article
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                © The Author(s) 2020


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