The major core histone antigenic determinants in systemic lupus erythematosus are in the trypsin‐sensitive regions

Abstract

Antibody responses against nucleosome core histones in systemic lupus erythematosus have been shown, by immunoblotting, to be directed largely against the trypsin-sensitive regions of the histones. These occur at the N-terminal regions of all 4 core histones and at the C-terminal ends of H2A and H3. Since these regions are often not the most antigenic when individual histones are used as immunogens, and appear to be exposed in the nucleosome, the active immunogens in systemic lupus erythematosus seem likely to be chromatin-bound, rather than free, histones. ChromatinHistone tail Anti-nuclear antibody Immunoblotting

Identification of New Pathogenic Players in Lupus: Autoantibody-Secreting Cells Are Present in Nephritic Kidneys of (NZBxNZW)F1 Mice

“…Using the two large cleavage H2B fragments 1-59 and 63-125 and sera from lupus patients, Hardin and Thomas also drew the same conclusion (22). Interestingly in this context, it has also been shown that the N-terminal region of H2B is readily exposed at the surface of mono-and polynucleosomes (29,38,39). The predominant reactivity toward this region of the core histone H2B is very likely to be directly correlated to its structural localization in the nucleosomal particle.…”

Autoantigenic histone epitopes: a comparison between procainamide‐ and hydralazine‐induced lupus

“…To insure reproducibility, immunoblots of patient sera were typically performed at least twice, all immunoblots were exposed to XRP film (Kodak, Rochester, NY) for 48 hours at -7O"C, and a positive serum and a normal control serum were included in each experiment. As noted previously, normal control sera either gave no binding or showed only faint background binding that did not reveal individual histones as distinct bands (5, 7). Test sera were scored as follows: + = distinct bands that were unequivocally Immunoblots of trypsinized and intact histones.…”

“…Whole histones were extracted from chick erythrocyte nuclei, as previously described (7). Histones lacking aminoand/or carboxyl-terminal ends were extracted with 0.2N H2S04 from chick erythrocyte nuclei that were previously digested with trypsin (7).…”

“…Antibodies to histones are also found in 3040% of patients with spontaneous systemic lupus erythematosus (SLE) (1,3-6), and the most common responses are directed against histones HI, H2B (5, 7,8), and to a lesser extent, H3 (6,7).…”

“…In contrast, patients with spontaneous SLE produce antibodies that bind histone H2B at its extreme amino-terminal end (5, 7,8); these antibodies often occur in linkage with antibodies to the carboxylterminal half of histone H1 (5). This focused antihistone response in patients with SLE raised the question of whether the antihistone antibodies associated with drug-induced lupus might recognize a similar set of histone epitopes.…”