Apoptosis-associated acetylation on histone H2B is an epitope for lupus autoantibodies

Bavel, Casandra C. van; Dieker, Jürgen; Muller, Sylviane; Briand, Jean‐Paul; Monestier, Marc; Berden, Jo H. M.; Vlag, Johan van der

doi:10.1016/j.molimm.2009.08.009

Cited by 92 publications

(73 citation statements)

References 30 publications

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“…In addition to the aforementioned, we describe in the current report that NETs from SLE patients contain many methylated and acetylated residues in their histones that may increase the immunostimulatory potential of NETs. We show that when neutrophils undergo NETosis, histones are highly susceptible to acetylation and methylation of certain residues that were reportedly associated with apoptosis [17][18][19][20]. Whereas histones from unstimulated viable SLE neutrophils are relatively hypoacetylated at H4-K8,12,16 and H2B-K12 and hypomethylated at H3-K27 (in concordance with earlier reported hypoacetylation and hypomethylation in splenocytes [26] and CD4 + T cells [27], respectively), they become hyperacetylated and hypermethylated upon NETosis.…”

Section: Discussionsupporting

confidence: 89%

“…We have described previously that specific histone modifications are associated with both apoptosis and the autoimmune response in patients with SLE [17][18][19][20]. In this report we investigated whether the same SLE-associated histone modifications are to be detected in NETs, as 70% of their proteins are histones.…”

Section: Introductionmentioning

confidence: 84%

“…After stimulation, neutrophils and NETs were suspended in paraformaldehyde (final concentration 1%) to a cell density of 1 × 10 6 per ml and then centrifuged at 800 g for 10 min with a cytospin cuvette (Hettich Cyto System, Tuttlingen, Germany) on glass slides. DNA was stained for 30 min with 1 μg/ml 4′,6-diamidino-2-phenylindole (DAPI) (Invitrogen, Eugene, OR, USA) and histones were stained employing our panel of lupus-derived monoclonal antibodies consisting of #34 (anti-H3; [17]), KM-2 (anti-H4-K8,12,16ac [18]), LG11-2 (anti-H2B-K12ac [19]) and BT164 (anti-H3-K27me3 [20]). The specificity of these four monoclonal antibodies was determined originally by epitope mapping using random peptide phage display.…”

Section: Visualization and Quantification Of Histone Modifications Inmentioning

confidence: 99%

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Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus

Pieterse

Hofstra

Berden

et al. 2014

Clinical and Experimental Immunology

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Original ArticleAcetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus OTHER ARTICLES PUBLISHED IN THIS SERIESDying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clinical and Experimental Immunology 2015, 179: 5-10. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16 SummaryIn addition to disturbed apoptosis and insufficient clearance of apoptotic cells, there is recent evidence for a role of neutrophils in the aetiopathogenesis of systemic lupus erythematosus (SLE). In response to various stimuli, neutrophils can rapidly release DNA fibres decorated with citrullinated histones and anti-microbial peptides. These structures are referred to as neutrophil extracellular traps (NETs). In addition to apoptotic cell-derived microparticles, these NETs may comprise a further source of autoantigens, able to drive the autoimmune response in SLE. Our group recently identified specific histone modifications occurring during apoptosis that play an important role in the autoimmune response in SLE. In the current study, we evaluated the presence and immunostimulatory potential of these previously identified histone modifications in NETs. Compared to NETs from healthy donors, the histones present in NETs formed by SLEderived neutrophils contain increased amounts of acetylated and methylated residues, which we previously observed to be associated with apoptosis and SLE. Treatment of neutrophils with histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), prior to induction of NETosis, induced NETs containing hyperacetylated histones, endowed with an increased capacity to activate macrophages. This implies that specific histone modifications, in particular acetylation, might enhance the immunostimulatory potential of NETs in SLE.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 84%

Section: Visualization and Quantification Of Histone Modifications Inmentioning

confidence: 99%

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Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus

Pieterse

Hofstra

Berden

et al. 2014

Clinical and Experimental Immunology

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“…When neutrophils undergo mitosis, histones are highly susceptible to acetylation and methylation of certain residues that were reportedly associated with apoptosis [16][17][18]. The increased content of acetylated and methylated residues on histones from NETs of SLE patients may, therefore, indirectly increase the immune-stimulatory potential of NETs via an enhanced binding of antimicrobial peptides within the NETs.…”

Section: Mechanism Of Diseasementioning

confidence: 99%

Ocular Manifestations in Systemic Lupus Erythematosus

Maghsoudlou¹

2015

Rheumatology (Sunnyvale)

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Systemic lupus erythematosus (SLE) is an autoimmune disease manifest with multiple organ system involvement. Even though the eye is not part of the diagnostic criteria, once it gets affected, it will alter patients' quality of life. The purpose of this review is to point out the significance of ocular manifestations in SLE and to emphasize the importance of possible blinding complications such as peripheral ulcerative keratitis, scleritis, and SLE retinopathy/ choroidopathy. The condition can be even worse when SLE is accompanied with antiphospholipid syndrome. In addition to the disease itself, several treatment agents that are used in SLE are responsible for vision threatening conditions; thus they have to be given with caution because of potential side effects, including cataract, glaucoma, and chloroquine maculopathy.

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“…Interestingly, histone post-translational modification areas correspond to major B and T cell epitopes, and critical "hot-spots" for autoAb recognition [80]. For example, the H4 derived peptide 1e22 acetylated on K 8,14,16 residues and the H2B derived peptide 1e18 acetylated on K 12 showed a superior reactivity when compared to the native peptide when using plasma from SLE patients or plasma from the SLE prone mouse model MRL/ lpr [87,88]. Using two mAbs specific for the acetylated H4 peptide (clone KM-2) and for the acetylated H2B peptide (clone LG11-2) an increased reactivity was demonstrated when histones were prepared from apoptotic cells instead of normal cells.…”

Section: Epigenetic Modifications and Autoantibodiesmentioning

confidence: 99%