Engulfed cell remnants, and not cells undergoing apoptosis, constitute the LE-cell phenomenon

Abstract

The LE cell has been one of the first immunological signs of active systemic lupus erythematosus, included into the ACR criteria. LE cells consist of a phagocyte engulfing material of disputed origin, which was interpreted as either cellular remnants from necrotic cells or as early apoptotic cells. It is well established that LE cell formation is dependent on autoantibodies against the linker histone H1. In view of this fact, we investigated whether anti-histone H1 antibodies and LE cell positive sera bound to cells where apoptosis had been induced by gliotoxin or actinomycin D or which were necrotic after heating. Necrotic cell remnants, but not (early) apoptotic cells were bound by anti-histone H1 antibodies and LE cell positive sera, establishing that the process of LE cell formation, which is dependent on anti-H1 binding, leads to engulfment of necrotic (or late apoptotic) material, but not of early apoptotic cells.

Linker Histone in Diseases

“…However, an inflammatory response against apoptotic bodies will take place if the process of phagocytosis is impaired, thus provoking autoimmunity (Figure 3 ) 75 . Specifically, the phagocytes that engulf linker histones will turn into LE cells, which is one of the signs for active SLE 76 . For patients that develop SLE, serum antibodies that target the C-terminal of the linker histone are often detected with high specificity 77 , 78 .…”

A variety of death modes of neutrophils and their role in the etiology of autoimmune diseases

“…These processes cause an inflammatory response, stimulate the surrounding immune cells, and further lead to tissue damage and disease progression 240,241 . Neutrophils necrosis can exist not only as a trigger, but also the outcome of disease development in the inflamed tissues of patients with autoimmune disease 242,243 . Since necrosis is often accompanied by apoptosis or other modes of death, there are few studies on its single and direct role in autoimmune diseases.…”

The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus: an observational longitudinal study

“…The first laboratory test proposed as a diagnostic tool for SLE was the lupus erythematosus (LE) cell, described in 1948 as a specific finding in bone marrow leukocytes in patients affected by SLE [ 19 ]. Further studies have shown that LE cells consist of mature PMNs in which the nucleus has been dislocated to the periphery of the cell after engulfment of antibody- and complement-opsonized nuclear material [ 20 , 21 ]. The presence of LE cells was included in the list of the classification criteria for SLE [ 14 , 17 ] and related to more severe clinical manifestations [ 22 , 23 ].…”