Nuclear antigen histone H1 is primarily involved in lupus erythematosus cell formation

Abstract

Objective. To elucidate the nature of the antigen reactive with the "lupus erythematosus (LE) cell factor," the autoantibody involved in the LE cell phenomenon.Methods. Serum samples from systemic lupus erythematosus (SLE) patients who were positive for the LE cell phenomenon (LEc+) and SLE patients who were negative for the LE cell phenomenon (LEc-) were used to characterize the nuclear antigen bound by the LE cell factor, by immunoblotting and immunoprecipitation techniques.Results. All LEc+ sera, but none of the LEcsera, uniformly reacted with a double band of M W -30 kd in nuclear extracts. Depletion of nuclear protein extracts of antigens bound by pooled LEc-serum allowed precipitation of a low molecular weight protein by pooled LEc+ serum. This protein was able to block LE cell formation by LEc+ serum. Based on its reactivity with antihistone antibody and an electrophoretic mobility identical with that of precipitated and purified histone H1, this protein was identified as histone H1. Moreover, all LEc+ sera, but none of the LEc-sera, reacted with purified histone H1 by immunoblotting, whereas other histones were reactive with both types of sera. In addition, purified histone H1, but none of the other histones, strongly inhibited the induction of LE cells by LEc+ serum.Conclusion. Histone H1 represents the major antigenic component recognized by the LE cell factor. Thus, the LE cell phenomenon appears to be due primarily to anti-histone H1 reactivity.The lupus erythematosus (LE) cell phenomenon was recognized 50 years ago by Hargraves et a1 (1) constituted one of the first laboratory abnormalities ever found to be associated with systemic lupus erythematosus (SLE). It requires the presence of cell nuclei released from traumatized cells that usually have lost the normal chromatin pattern (2), antibodies originally termed LE cell factor (3), and complement (4). The ensuing engulfment of the opsonized nuclear material by polymorphonuclear cells leads to the classic appearance of the LE cell.After its original description, the elucidation of the mechanisms responsible for and related to LE cell formation became the center of interest for a generation of immunologists and rheumatologists. Kunkel, Holman, and Deicher observed that the LE cell factor was reactive with deoxyribonucleoproteins of the cell nucleus (5-7) and that it could be associated with pathologic events in SLE (8,9). Thus, the LE cell phenomenon was the first antinuclear antibody reactivity ever described and gave rise to a still-growing list of known autoantibodies to nuclear constituents. Meanwhile, several dozen nuclear antigens have been characterized and shown to react with autoantibodies from patients with SLE and various other rheumatic diseases (10-13).In spite of these advances, the autoantigen reactive with the LE cell factor has not been characterized, and the reactivities of the LE cell factor that are best known to date are the originally described and later confirmed ones with nucleosomes (5-7,14,15) which contain DNA and histones...

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

“…Uptake of necrotic cell material into PMNs in SLE patients was first described in 1948 by Hargraves et al (33) and is mediated by autoantibodies and Fc␥R (34). In this study, EndoS-treated SLE sera lost their capability to mediate phagocytosis of the necrotic cell material to PMNs.…”

“…The ability of SLE serum to support the uptake of necrotic cell material into PMNs, also called the lupus erythematosus cell phenomenon, was first described in bone marrow from SLE patients by Hargraves et al in 1948 (33). It is known that this is an autoantibody-and Fc␥R-mediated process (34). We investigated whether EndoS treatment inhibited the phagocytosis of ICs to PMNs and the subsequent oxidative burst.…”

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…Similar to anti-DNA Abs, anti-nucleosomal Abs and AHA correlate with lupus disease activity [24e26], particularly Abs to histone H1, which appear to be more specific for SLE than other AHA [18,20]. Of note, it is anti-H1 Abs that are responsible for the LE cell phenomenon, which was originally included into the American College of Rheumatology (ACR) classification criteria for SLE [27,28].…”

Cross-recognition between histones and La/SSB may account for anti-DNA reactivity in SLE patients

“…Because histone H1 is localized at the outer face of the nucleosome, it may be more accessible to antibodies than the remaining histones. Actually in SLE, histone H1 has been considered as an autoantigen and has been implicated as the major target protein accounting for the Lupus Erythematosus Cell (L.E.C) phenomenon [12][13][14]. Although anti-histone H1 antibodies are very common in SLE, they are also found in other systemic autoimmune diseases, including SS and RA [15].…”