Many of the specific post translational histone modifi cations enriched in NETs overlapped those to which promotion information sig nificant autoreactivity is seen in a subset of patients with SLE. Nonetheless, this overlap was partial, and many PTMs distinguished NETs from SLE autoreactivity pro files. Further, while NETs were observed to be modestly immunogenic in vivo, the induced serological autoim mune responses were distinct from those observed in patients with lupus, as well as autoimmune prone MRL lpr mice. Conclusions In summary, to investigate the link between NETs and SLE, using histone PTMs as prospective biomarkers, we investigated the serum reactivity profile to a panel of histone PTMs in a cohort of SLE patients and identified significant autoantibody reactivity to acetyl histone H2B.

We devised a methodology to culture myeloid cell lines to Inhibitors,Modulators,Libraries produce NETs, and found that their PTMs indicate a state of transcriptionally silent chromatin that has decondensed with the aid of citrullination, a result of the NETosis process. Some of the human SLE serum reactivity overlaps with PTMs found on NETs, however, the presence of autoantibodies against acetyl histone H2B is discordant with the decrease in histone H2B acetylation in NETs. Furthermore, murine cell line derived NETs are weak immunogens in vivo. This result suggests that the breaking of tolerance to self Inhibitors,Modulators,Libraries requires more than a simple exposure to NETs. Introduction Neutrophil Inhibitors,Modulators,Libraries extracellular traps were first described in 2004 as web like structures that trap and neutralize microbes at sites of infection.

Neutrophils, a first line of defense against microorganisms during such encounters, produce these highly modified chroma tin webs through a cellular suicide program distinct from apoptosis and necrosis, termed NETosis. In addition to neutrophil antimicrobial proteins, NETs are comprised of Inhibitors,Modulators,Libraries chromatin components, including histones. Because NETs are extracellular and typically in an inflammatory environment, their proximity to compo nents of the adaptive and innate immune systems might provide an immunogenic substrate for autoimmune responses during regular encounters with commensal and pathogenic microbes. Indeed, an emerging and growing body of literature supports a putative link between NETs and autoimmu nity. Baker et al. identified circulating NETs in the blood of pediatric patients with malaria, a subset of whom also exhibited signs of an autoimmune response.

A more recent study Inhibitors,Modulators,Libraries identified a subset of patients with lupus nephritis whose sera were impaired in degrading NETs, suggesting that such impairment could be pathogenic. Two recent studies reported activa tion of plasmacytoid dendritic cells by com plexes between NETs and antimicrobial peptides such as LL 37 that engage Toll like receptor 9 and selleck products result in Type I interferon production, a process known to be associated with SLE.