title: Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis.
abstract: Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis.
authors: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jürgen
authors: J
authors: Dieker
authors: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jo H
authors: JH
authors: Berden
authors: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Marinka
authors: M
authors: Bakker
authors: CNRS, Immunopathologie et chimie thérapeutique/Laboratory of excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Jean-Paul
authors: JP
authors: Briand
authors: CNRS, Immunopathologie et chimie thérapeutique/Laboratory of excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Sylviane
authors: S
authors: Muller
authors: Department of Rheumatology and Clinical Immunology, and the Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg/Breisgau, Germany.
authors: Reinhard
authors: R
authors: Voll
authors: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors: Christopher
authors: C
authors: Sjöwall
authors: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Martin
authors: M
authors: Herrmann
authors: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Luuk B
authors: LB
authors: Hilbrands
authors: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Johan
authors: J
authors: van der Vlag
mesh_terms: D000107:Acetylation; D000328:Adult; D000595:Amino Acid Sequence; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006657:Histones / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008181:Lupus Nephritis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012372:ROC Curve
chemical_list: D001323:Autoantibodies; D006657:Histones; D010455:Peptides