Fine specificity mapping of autoantigens targeted by anti-centromere autoantibodies

Yasmin Akbarali, Jennifer Matousek-Ronck, Laura Hunt, Leslie Staudt, Morris Reichlin, Joel M. Guthridge, Judith A. James

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Autoantibodies to centromeric proteins are commonly found in sera of limited scleroderma and other rheumatic disease patients. To better understand the inciting events and possible pathogenic mechanisms of these autoimmune responses, this study identified the common antigenic targets of CENP-A in scleroderma patient sera. Utilizing samples from 263 anti-centromere immunofluorescence positive patients, 93.5% were found to have anti-CENP-A reactivity and 95.4% had anti-CENP-B reactivity by ELISA. Very few patient samples exclusively targeted CENP-A (2.7%) or CENP-B (4.2%). Select patient sera were tested for reactivity with solid phase overlapping decapeptides of CENP-A. Four distinct epitopes of CENP-A were identified. Epitopes 2 and 3 were confirmed by additional testing of 263 patient sera by ELISA for reactivity with these sequences constructed as multiple antigenic peptides. Inhibition CENP-A Western blots also confirmed the specificity of these humoral peptide immune responses in a subset of patient sera. The first three arginine residues (aa 4-6) of CENP-A appear essential for antibody recognition, as replacing these arginines with glycine residues reduced antibody binding to the expressed CENP-A protein by an average of 93.2% (range 80-100%). In selected patients with serial samples spanning nearly a decade, humoral epitope binding patterns were quite stable and showed no epitope spreading over time. This epitope mapping study identifies key antigenic targets of the anti-centromere response and establishes that the majority of the responses depend on key amino-terminal residues.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalJournal of Autoimmunity
Issue number4
StatePublished - Dec 2006
Externally publishedYes


  • Anti-centromere autoantibodies
  • Epitope mapping
  • Scleroderma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Fine specificity mapping of autoantigens targeted by anti-centromere autoantibodies'. Together they form a unique fingerprint.

Cite this