NDLI: Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

Content Provider	Springer Nature : BioMed Central
Author	Liu, Chih Long Tangsombatvisit, Stephanie Rosenberg, Jacob M Mandelbaum, Gil Gillespie, Emily C Gozani, Or P Alizadeh, Ash A Utz, Paul J
Abstract	Introduction Autoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. Methods We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. Results We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. Conclusions Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
Related Links	https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar3707.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14786362
DOI	10.1186/ar3707
Journal	Arthritis Research & Therapy
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2012-02-02
Access Restriction	Open
Subject Keyword	Rheumatology Orthopedics Systemic Lupus Erythematosus Systemic Lupus Erythematosus Patient Phorbol Myristate Acetate Neutrophil Extracellular Trap Autoantibody Profile
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology
Journal Impact Factor	4.4/2023
5-Year Journal Impact Factor	4.9/2023

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Erratum to: Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

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Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

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Erratum to: Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies

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