Molecular Biology Reports

, Volume 23, Issue 3–4, pp 147–151

Epitope analysis of chromo antigen and clinical features in a subset of patients with anti-centromere antibodies

  • Yoshinao Muro
  • Taku Yamada
  • Teruki Iwai
  • Kenji Sugimoto
Autoantibodies as Clinical Markers
  • 22 Downloads

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.

Key words

anti-centromere antibodies anti-chromo antibodies autoepitope chromo domain chromo shadow domain 

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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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Yoshinao Muro
    • 1
  • Taku Yamada
    • 2
  • Teruki Iwai
    • 1
  • Kenji Sugimoto
    • 2
  1. 1.Department of DermatologyNagoya University School of MedicineNagoyaJapan
  2. 2.Laboratory of Applied Molecular Biology, Department of Applied BiochemistryUniversity of Osaka PrefectureOsakaJapan

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