Isolation of anti-nucleosome antibodies from the plasma of lupus nephritis patients

Abstract

Anti-nucleosome antibodies, which recognise conformational epitopes consisting of histone and DNA in chromatin, have been described in autoimmune diseases. In this study, an attempt was made to isolate anti-nucleosome antibodies from the anti-DNA-depleted plasma IgG of two lupus patients either with or without nephritis by nucleohistone affinity chromatography. The purified nucleohistone-binding antibodies bound to nucleohistone in a specific manner and contained enriched anti-histone antibodies. However, adsorption of the purified antibodies with histone revealed that the nephritis patient-derived antibodies contained nucleohistone-specific antibodies. Although such purified antibodies may not recognise native structures of nucleosomes, this chromatography may provide a method to isolate and determine the fine specificity of anti-nucleosome antibodies in various autoimmune diseases.

Anti-Nucleosome Antibodies - A Novel Test in Systemic Lupus Erythematosus

“…The high levels of anti-nucleosome antibodies were also found in patients with lupus nephritis regardless of their overall disease activity. It supports the concept of nucleosome and anti-nucleosome complexes as the major pathogenic agent in lupus nephritis 2,9,17,18 . One of the most striking features of SLE is the production of auto-antibodies targeting the chromatin components as deoxyribonucleic acid, ribonucleic acid and histones.…”

“…Currently, the evidence has accumulated on the important role, which defect apoptosis might play in SLE pathogenesis 3,6,7 . At the same time the attention is attracted to the nucleosome 8,9 , the unit of chromatin and the product of cell apoptosis. The nucleosome consists of the core particle composed of an octamer of histones around which the helical DNA is wrapped and histone H1, which is located at the point, where DNA enters and exits the nucleosome 10 .…”

Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells

“…To determine whether E 2 increases survival of anti-DNA B cells and up-regulates production of anti-DNA antibodies, female R4A-␥2b transgenic BALB͞c mice were implanted with P or E 2 pellets designed to release between 75 and 100 pg͞ml of 17␤-estradiol into the circulation for up to 60 days. Sera assayed by RIA displayed average E 2 concentrations of 16 pg͞ml (range, in both E 2 -and P-treated mice at week 0 and 94 pg͞ml (range, 50-130) in E 2 -treated mice and 24 pg͞ml (range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] in P-treated mice by 5 weeks of treatment.…”

Antinucleosomal antibodies in systemic lupus erythematosus

“…Ряд авторов ука зывает на то, что данных о четкой ассоциации между эти ми антителами и обострениями СКВ и/или конкретными проявлениями болезни в настоящее время немного, а име ющиеся -противоречивы [20,28].…”

“…Аналогично этому, нуклеосом-специ-фичные антитела при СКВ связаны с нуклеосомами, осво божденными из апоптозных мононуклеарных клеток [28]. И наконец, в связи с тем, что считается, что С-реактивный белок (СРБ) способствует удалению ядерного материала из клеток апоптоза, оценивали влияние СРБ на клиренс нук леосом у нормальных BALB/c мышей [10].…”