Non-kinetochore directed autoantibodies in scleroderma/CREST. Identification of an activity recognizing a metaphase...

Three scleroderma/CREST sera possessing anti-kinetochore autoantibody were tested by indirect immunofluorescence for reaction with isolated Chinese hamster metaphase chromosomes and histone-dissociated chromosome "scaffolds". All three sera revealed kinetochore staining on both whole chromosomes and histone-dissociated chromosomes, and confirmed previous reports that the kinetochore is part of the chromosome scaffold. Unexpectedly, one serum also recognized a non-centromere-located chromosomal antigen which is retained at the axial non-histone protein core following histone dissociation. The antigen is exclusively nuclear in origin, does not appear to be DNA or residual histone, and seems to correspond to a major component of the chromosome core. The existence of this antigen has important implications in terms of chromosome structure. Another CREST serum was shown to possess autoantibody against a cytoplasmic structural component, in addition to anti-kinetochore activity. The presence of anti-kinetochore and other autoantibody activities in CREST patient sera is discussed in relation to disease processes.