Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype Academic Article uri icon

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abstract

  • We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p=.004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p=.024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606-614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.

authors

  • Fritzler, Marvin J
  • Hudson, Marie
  • Choi, May Y
  • Mahler, Michael
  • Wang, Mianbo
  • Bentow, Chelsea
  • Milo, Jay
  • Baron, Murray
  • Pope, J
  • Baron, M
  • Markland, J
  • Robinson, D
  • Jones, N
  • Khalidi, Nader
  • Docherty, P
  • Kaminska, E
  • Masetto, A
  • Sutton, E
  • Mathieu, J-P
  • Hudson, M
  • Ligier, S
  • Grodzicky, T
  • LeClercq, S
  • Thorne, C
  • Gyger, G
  • Smith, D
  • Fortin, PR
  • Larché, M
  • Abu-Hakima, M
  • Rodriguez-Reyna, TS
  • Cabral, AR
  • Fritzler, MJ

publication date

  • March 2018