The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody specificity in lupus erythematosus cell-positive and -negative sera

Objective To compare and investigate antihistone and antichromatin antibody responses as well as clinical variables in patients with systemic lupus erythematosus (SLE) who were either positive (LEC+) or negative (LEC−) for the lupus erythematosus (LE) cell phenomenon. Methods The binding properties of LEC+ and LEC− SLE sera to chromatin-associated nuclear antigens (histones H1, H2A, H2B, H3, H4; complexes of H2A–H2B, [H2A–H2B]–DNA, H1–DNA; total and H1-stripped chromatin; native and denatured DNA) were investigated. In addition, sera from patients with drug-induced lupus (by procainamide, hydralazine, or quinidine), as well as from patients with rheumatoid arthritis and osteoarthritis, were assessed. Enzyme-linked immunosorbent assay was used to detect specific antibody binding. Results Mirroring the important role of histone H1 in the formation of LE cells, anti–histone H1 reactivity was 8-fold higher in LEC+ sera than in LEC− sera. In addition, reactivities to most of the other antigens tested, i.e., other histones and histone–DNA complexes as well as chromatin and DNA, were significantly higher in LEC+ sera than in LEC− sera. All but 1 serum sample from the patients with drug-induced lupus were negative for LE cell formation as well as for anti–histone H1 reactivity, but displayed high antibody reactivities to histone–DNA complexes, including chromatin. Sera from patients with rheumatoid arthritis and osteoarthritis did not show significant binding to these antigens. When comparing the clinical features of LEC+ and LEC− SLE patients, severe organ involvement, including nephritis and central nervous system involvement, was common in the LEC+ group, but rare in the LEC− group. Conclusion A positive LE cell phenomenon not only correlated with the presence of high anti–histone H1 antibody levels in SLE, but also indicated serologically and clinically active disease with major organ involvement.