title: Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?
abstract: The objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with urinary CD4(+) effector memory T cells and urinary monocyte chemoattractant protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy controls (HC) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB1 were measured by Western blot. CD4(+) T cells and CD4(+) effector memory T cells (CD4(+) CD45RO(+) CCR7(-) ) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1 and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1 in urine than HC [10·3 (7·05-18·50) versus 5·8 (4·48-7·01); P = 0·004]. Both urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to remission. The urinary MCP-1/creatinine ratio correlated with Birmingham Vasculitis Activity Score (BVAS) (P = 0·042). No correlation was found between the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation was found between urinary HMGB1/creatinine ratio and CD4(+) T cells/creatinine ratio (P = 0·028) and effector memory T cells/creatinine ratio (P = 0·039) in urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB1 levels are associated with CD4(+) T cells and CD4(+) effector memory T cells in urine. Measurement of urinary HMGB1 may be of additional value in identifying active glomerulonephritis in AAV patients.
authors: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Rheumatology Division, Department of Internal Medicine, Universidade Federal de São Paulo/Escola Paulista de Medicina (Unifesp/EPM), São Paulo, Brazil.
authors: A W S
authors: AW
authors: de Souza
authors: W H
authors: WH
authors: Abdulahad
authors: P
authors: P
authors: Sosicka
authors: J
authors: J
authors: Bijzet
authors: P C
authors: PC
authors: Limburg
authors: C A
authors: CA
authors: Stegeman
authors: M
authors: M
authors: Bijl
authors: J
authors: J
authors: Westra
authors: C G M
authors: CG
authors: Kallenberg
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000652:urine; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000209:etiology* / Q000652:urine*; D024243:HMGB1 Protein / Q000097:blood / Q000652:urine*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D024243:HMGB1 Protein
keywords: HMGB1; T cells; anti-neutrophil cytoplasmic antibody-associated vasculitis; glomerulonephritis; monocyte chemoattractant protein-1