SUMMARYAnti-chromo antibodies (AChA) are autoantibodies accompanying anti-centromere antibodies (ACA). We determined the frequency and clinical significance of AChA in autoimmune rheumatic diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and with recombinant N-terminus of 25-kD chromo protein (p25). AChA were detected in 28 (36%) of 77 sera with ACA. AChA were found only in ACA-positive sera. Twenty-two (79%) of 28 recognized a recombinant N-terminal portion of p25, including the chromo domain which is conserved among species. AChA were related to leucopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, and existence of Sjögren's syndrome (SS). In ACA-positive patients, AChA might be a serologic indicator of systemic sclerosis (SSc), having features of systemic lupus erythematosus and/or SS or diseases other than SSc.
Heterochromatin protein 1 (HP1) is one of the nonhistone chromosomal components tightly associated with the pericentromeric heterochromatic region in Drosophila. The human homologue of HP1 is recognized by a subpopulation of anti-centromere antibodies (ACA). Such autoantibodies recognize a group of several nuclear proteins with Mr of 23-25 kDa and have been termed 'anti-chromo antibodies (AChA)' because an evolutionarily conserved N-terminal half called the 'chromo domain' of HP1 is the epitope. In this study, 84 ACA sera were examined by immunoblotting with recombinant 25-kDa chromo protein (p25). The p25 antigen was expressed as a glutathione S-transferase-fusion protein in E. coli and purified with glutathione-sepharose. Except for one serum specimen, AChA-positive sera reacted with the N-terminus (a.a 16-106) and/or the C-terminus (a.a. 83-191) of p25. Autoimmune response against the N-terminus of p25 in 33 patients was significantly associated with systemic lupus erythematosus and significantly related to leukopenia, thrombocytopenia and elevated erythrocyte sedimentation rate; C-terminal reactivity in 30 patients was significantly associated with primary Sjogren's syndrome and related to leukopenia. The internal 64-amino acid stretch (a.a 43-106) with DNA-binding activity was not autoantigenic. p25 has two separate homologous regions to Drosophila HP1 at the N- and C-termini; the chromo domain and the chromo shadow domain. Patients with autoimmune response against these conserved domains might form a clinical subset of patients positive for ACA.
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