A Autoantibodies Specific for Histone

Previous studies have ident i f ied two sets of h u m a n au toan t ibod ies with a p p a r e n t dual specifici ty (1-6). T h e first set reacts with the Fc f ragment of IgG (1, 2) and with an an t igen ic d e t e r m i n a n t on core mononucleosomes, the repea t ing h i s tone-DNA subuni t of ch roma t in (3). T h e o ther set, which is the subject of the present report , recognizes a p l a sma m e m b r a n e ant igen of nuc lea ted cells (4, 5) and an ant igen on core mononucleosomes (6), but not IgG. Some of these observat ions have been conf i rmed by others (7-9). T h e second set, which has been cal led X A N A (for cross-react ing an t i -nuc lea r ant ibodies) , is found in the sera of pa t ien ts wi th systemic lupus e ry thematosus (SLE) x and re la ted diseases. It is ident i f ied and pa r t i a l ly pur i f ied by incuba t ion of serum with v iable h u m a n leucocytes at 37°C, and the absorbed ant ibodies are then eluted; the fract ion of the e lua te wi th fluorescence an t inuc lea r an t ibody (ANA) act iv i ty represents c rossreac t ive-ANA (X-ANA) (4). Because 75-90% of the A N A act iv i ty can be absorbed by viable cells (4), it is evident tha t X A N A comprise a ma jo r fract ion of A N A in these sera. In this repor t we will present evidence that X A N A from two pat ien ts recognize an ep i tope on the isolated oc t amer of the four inner histones in 2 M salt, and that XA N A do not dis t inguish between na t ive nucleosomes and nucleosomes reassembled from D N A a n d inner his tone octamers. T h e f indings will be discussed in terms of cur rent concepts of ch roma t in s t ructure and dual specificity of ant ibodies .