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Autoantibodies agai...
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Dieker, JurgenRadboud University of Nijmegen, Netherlands
(author)
Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-10-25
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PUBLIC LIBRARY SCIENCE,2016
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-133399
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-133399URI
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https://doi.org/10.1371/journal.pone.0165373DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies|Dutch Arthritis Association [09-1-308]; German Research Society (DFG) [SFB643-TP-B5]; K & R Wucherpfennig-Stifting; French Centre National de la Recherche Scientifique; Laboratory of Excellence Medalis, Initiative of Excellence (IdEx), Strasbourg University [ANR-10-LABX-0034]
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Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of antichromatin/ 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 (H4p(ac)), H2B peptide acetylated at lysine 12 (H2Bp(ac)), H3 peptide trimethylated at lysine 27 (H3p(me)), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4p(ac) showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bp(ac) exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3p(me) appeared not specific for SLE. Anti-H4p(ac) and anti-H2Bp(ac) 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/H2Bp(ac) and a more pronounced reactivity with the modified equivalent of H3p(me) and H2Bp(ac). In conclusion, reactivity with H4p(ac) and H2Bp(ac) is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bp(ac) is in particular associated with lupus nephritis.
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Berden, Jo H.Radboud University of Nijmegen, Netherlands
(author)
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Bakker, MarinkaRadboud University of Nijmegen, Netherlands
(author)
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Briand, Jean-PaulCNRS, France
(author)
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Muller, SylvianeCNRS, France
(author)
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Voll, ReinhardUniversity of Medical Centre Freiburg, Germany; University of Medical Centre Freiburg, Germany
(author)
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Sjöwall, ChristopherLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)chrsj93
(author)
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Herrmann, MartinFriedrich Alexander University of Erlangen Nuremberg, Germany
(author)
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Hilbrands, Luuk B.Radboud University of Nijmegen, Netherlands
(author)
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van der Vlag, JohanRadboud University of Nijmegen, Netherlands
(author)
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Radboud University of Nijmegen, NetherlandsCNRS, France
(creator_code:org_t)
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In:PLOS ONE: PUBLIC LIBRARY SCIENCE11:101932-6203
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Berden, Jo H.
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Voll, Reinhard
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