title: Mapping urinary chemokines in human lupus nephritis: Potentially redundant pathways recruit CD4+and CD8+T cells and macrophages.
abstract: Renal infiltration of inflammatory cells contributes to the pathogenesis of lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity. Analysis of the corresponding receptors revealed abundance of urinary CD8+T cells for CCR5 and CXCR3, while CD4+T cells were additionally enriched for CCR1, CCR6 and CXCR6. Urinary Treg showed similar CCR expression, and urinary CD14+macrophages were enriched for CCR5 expressing cells. In conclusion, cell specific recruitment patterns seem to involve CCR5 and CXCR3 in all cells studied, while CD4+T-cell subset recruitment is probably much more varied. However, urinary chemokine abundance in active LN is individually variable in our cohort and does not offer a singular chemokine usable as universal biomarker or potential future treatment target.
authors.affiliation: Department of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Klocke
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kopetschke
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna-Sophie
authors.initials: AS
authors.lastname: Grießbach
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Langhans
authors.affiliation: Department of Rheumatology, Universitätsklinikum Schleswig Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Jens Y
authors.initials: JY
authors.lastname: Humrich
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Biesen
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.affiliation: German Rheumatism Research Center (DRFZ), Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Rheumatology, Universitätsklinikum Schleswig Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: Department of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Enghard
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000097:blood / Q000652:urine*; D002633:Chemotaxis / Q000276:immunology; D016000:Cluster Analysis; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007958:Leukocyte Count; D008181:Lupus Nephritis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000652:urine*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D012372:ROC Curve; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D016482:Urinalysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D019707:Receptors, Chemokine
keywords: Biological markers; Chemokines; Lupus nephritis; Systemic lupus erythematosus (SLE); T-Lymphocytes; Urinary chemokines