TY - JOUR T1 - The role of microparticles in the pathogenesis of SLE: a new look at an old paradigm JF - Lupus Science & Medicine DO - 10.1136/lupus-2017-000220 VL - 4 IS - 1 SP - e000220 AU - David Pisetsky Y1 - 2017/10/01 UR - http://lupus.bmj.com/content/4/1/e000220.abstract N2 - Winberg et al 1 present important new information on a story that began with the discovery of the lupus erythematosus (LE) cell phenomenon. As described in a truly landmark paper, Hargraves and colleagues established the existence of the LE cell phenomenon using bone marrow specimens from patients with SLE. The LE cell reflects the unique immune environment in SLE and is basically a cell nucleus that has been opsonised by an ANA and complement and is then engulfed by a neutrophil.2 The key players for this phenomenon (nucleus, ANA, complement, phagocyte) remain at the centre of lupus research today, a rare example of a paradigm that has barely shifted or wobbled during the course of many decades.In the study of the LE cell, the nucleus has received much less attention than the other players which, after all, are usual blood components. In ordinary circumstances, the nucleus resides within the safe confines of the cell; with the exception of physiological enucleation during red blood cell maturation, nuclei do not transit into the extracellular milieu. In contrast, nuclear material including chromatin and its DNA and histone components can readily leave cells during the pounding and crushing of cells as they die.3 In the current model of lupus pathogenesis, excessive cell death or insufficient dead cell clearance leads to a large flux of nuclear material into the blood to form immune complexes (ICs) or drive autoreactivity.4 Despite much peering into microscopes, investigators have produced little decisive evidence for the extracellular translocation of nuclei during cell death. Studies indicate that nuclear material rather than exiting the cell as an intact nucleus, undergoes relocation, rearrangement and repackaging to form apoptotic bodies and microparticles. An apoptotic body is the collapsed remnant of an apoptotic cell or a large fragment that has broken off as apoptotic … ER -