Epitope analysis of chromo antigen and clinical features in a subset of patients with anti-centromere antibodies.
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.
Muro
Y
Y
Department of Dermatology, Nagoya University School of Medicine, Japan.
Yamada
T
T
Iwai
T
T
Sugimoto
K
K
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D002503:Centromere / Q000276:immunology*; D000090266:Chromobox Protein Homolog 5; D004330:Drosophila; D018604:Epitope Mapping; D006570:Heterochromatin / Q000276:immunology*; D006801:Humans
D000974:Antibodies, Antinuclear; D001324:Autoantigens; C000715594:CBX5 protein, human; D006570:Heterochromatin; D000090266:Chromobox Protein Homolog 5