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dc.contributor.authorDwivedi, Nishant
dc.contributor.authorUpadhyay, Jagriti
dc.contributor.authorNeeli, Indira
dc.contributor.authorKhan, Salar
dc.contributor.authorPattanaik, Debendra
dc.contributor.authorMyers, Linda
dc.contributor.authorKirou, Kyriakos A.
dc.contributor.authorHellmich, Bernhard
dc.contributor.authorKnuckley, Bryan
dc.contributor.authorThompson, Paul R
dc.contributor.authorCrow, Mary K.
dc.contributor.authorMikuls, Ted R.
dc.contributor.authorCsernok, Elena
dc.contributor.authorRadic, Marko
dc.date2022-08-11T08:11:00.000
dc.date.accessioned2022-08-23T17:28:12Z
dc.date.available2022-08-23T17:28:12Z
dc.date.issued2012-04-01
dc.date.submitted2015-05-22
dc.identifier.citationArthritis Rheum. 2012 Apr;64(4):982-92. doi: 10.1002/art.33432. Epub 2011 Oct 27. <a href="http://dx.doi.org/10.1002/art.33432">Link to article on publisher's site</a>
dc.identifier.issn0004-3591 (Linking)
dc.identifier.doi10.1002/art.33432
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50027
dc.description<p>At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.</p>
dc.description.abstractOBJECTIVE: To test the hypothesis that autoantigen modifications by peptidylarginine deiminase type 4 (PAD-4) increase immunoreactivity. METHODS: We assembled sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Felty's syndrome (FS), and antineutrophil cytoplasmic antibody-associated vasculitides (AAVs), as well as sera from control subjects without autoimmune diseases. The sera were tested for binding to activated neutrophils, deiminated histones, and neutrophil extracellular chromatin traps (NETs). IgG binding to lipopolysaccharide-activated neutrophils was assessed with confocal microscopy, and binding to in vitro-deiminated histones was measured using enzyme-linked immunosorbent assay (ELISA) and Western blotting. In addition, we quantitated histone deimination in freshly isolated neutrophils from the blood of patients and control subjects. RESULTS: Increased IgG reactivity with activated neutrophils, particularly binding to NETs, was paralleled by preferential binding to deiminated histones over nondeiminated histones by ELISA in a majority of sera from FS patients but only in a minority of sera from SLE and RA patients. Immunoblotting revealed autoantibody preference for deiminated histones H3, H4, and H2A in most FS patients and in a subset of SLE and RA patients. In patients with AAVs, serum IgG preferentially bound nondeiminated histones over deiminated histones. Increased levels of deiminated histones were detected in neutrophils from RA patients. CONCLUSION: Circulating autoantibodies in FS are preferentially directed against PAD-4-deiminated histones and bind to activated neutrophils and NETs. Thus, increased reactivity with modified autoantigens in FS implies a direct contribution of neutrophil activation and the production of NET-associated nuclear autoantigens in the initiation or progression of FS.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22034172&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/art.33432
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
dc.subjectArthritis, Rheumatoid
dc.subjectAutoantibodies
dc.subjectAutoantigens
dc.subjectFelty Syndrome
dc.subjectFemale
dc.subjectHistones
dc.subjectHumans
dc.subjectLupus Erythematosus, Systemic
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectNeutrophils
dc.subjectBiochemistry
dc.subjectEnzymes and Coenzymes
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectMusculoskeletal Diseases
dc.subjectTherapeutics
dc.titleFelty's syndrome autoantibodies bind to deiminated histones and neutrophil extracellular chromatin traps.
dc.typeJournal Article
dc.source.journaltitleArthritis and rheumatism
dc.source.volume64
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/thompson/37
dc.identifier.contextkey7135703
html.description.abstract<p>OBJECTIVE: To test the hypothesis that autoantigen modifications by peptidylarginine deiminase type 4 (PAD-4) increase immunoreactivity.</p> <p>METHODS: We assembled sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Felty's syndrome (FS), and antineutrophil cytoplasmic antibody-associated vasculitides (AAVs), as well as sera from control subjects without autoimmune diseases. The sera were tested for binding to activated neutrophils, deiminated histones, and neutrophil extracellular chromatin traps (NETs). IgG binding to lipopolysaccharide-activated neutrophils was assessed with confocal microscopy, and binding to in vitro-deiminated histones was measured using enzyme-linked immunosorbent assay (ELISA) and Western blotting. In addition, we quantitated histone deimination in freshly isolated neutrophils from the blood of patients and control subjects.</p> <p>RESULTS: Increased IgG reactivity with activated neutrophils, particularly binding to NETs, was paralleled by preferential binding to deiminated histones over nondeiminated histones by ELISA in a majority of sera from FS patients but only in a minority of sera from SLE and RA patients. Immunoblotting revealed autoantibody preference for deiminated histones H3, H4, and H2A in most FS patients and in a subset of SLE and RA patients. In patients with AAVs, serum IgG preferentially bound nondeiminated histones over deiminated histones. Increased levels of deiminated histones were detected in neutrophils from RA patients.</p> <p>CONCLUSION: Circulating autoantibodies in FS are preferentially directed against PAD-4-deiminated histones and bind to activated neutrophils and NETs. Thus, increased reactivity with modified autoantigens in FS implies a direct contribution of neutrophil activation and the production of NET-associated nuclear autoantigens in the initiation or progression of FS.</p>
dc.identifier.submissionpaththompson/37
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages982-92


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