Abstract
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 responses against these conserved domains might form a clinical subset of patients positive for ACA.
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Abbreviations
- ACA:
-
anti-centromere antibodies
- AChA:
-
anti-chromo antibodies
- CENP:
-
centromere protein
- DM:
-
dermatomyositis
- ESR:
-
erythrocyte sedimentation rate
- GST:
-
glutathione S-transferase
- HP1:
-
heterochromatin protein 1
- p25:
-
25-kDa chromo protein
- SLE:
-
systemic lupus erythematosus
- SS:
-
Sjogren's syndrome
- SSc:
-
systemic sclerosis
- WBC:
-
white blood cell
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Muro, Y., Yamada, T., Iwai, T. et al. Epitope analysis of chromo antigen and clinical features in a subset of patients with anti-centromere antibodies. Molecular Biology Reports 23, 147–151 (1996). https://doi.org/10.1007/BF00351162
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DOI: https://doi.org/10.1007/BF00351162