C1D is a major autoantibody target in patients with the polymyositis-scleroderma overlap syndrome

Arthritis Rheum. 2007 Jul;56(7):2449-54. doi: 10.1002/art.22710.

Abstract

Objective: To assess whether the recently discovered exosome-associated proteins MPP6, C1D, KIAA0052/hMtr4, hSki2, and hSki8 are targeted by autoantibodies, and to determine whether these autoantibodies are accompanied by antibodies directed to the established exosome-associated autoantigens PM-Scl-75 and PM-Scl-100.

Methods: Complementary DNAs encoding the recently identified human exosome-associated proteins were expressed as His-tagged fusion proteins in Escherichia coli cells. Sera obtained from patients with several different autoimmune diseases were analyzed for the presence of autoantibodies directed to these proteins, in an enzyme-linked immunosorbent assay (ELISA). The ELISA data obtained for C1D were confirmed by Western blot analysis, using recombinant C1D.

Results: All exosome-associated proteins were found to be targeted by autoantibodies, although the frequency with which such antibodies occurred in patient sera was relatively low, with the exception of anti-C1D antibodies. Autoantibodies recognizing C1D were detected in 7 of 30 patients (23%) with the polymyositis (PM)-scleroderma overlap syndrome; this frequency was similar to the frequencies for the established autoantigens PM-Scl-75c (27%) and PM-Scl-100 (23%). Importantly, several patients with the PM-scleroderma overlap syndrome had anti-C1D antibodies but no anti-PM-Scl antibodies. Anti-C1D autoantibodies were observed in only 2 of 204 patients with other diseases, including PM, dermatomyositis, and scleroderma.

Conclusion: Our results demonstrate that the recently identified exosome-associated protein C1D is a major autoantigen in patients with the PM-scleroderma overlap syndrome and suggest that the use of recombinant C1D as an autoantibody target may aid in diagnosis of the PM-scleroderma overlap syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies
  • Autoantigens / immunology
  • Co-Repressor Proteins
  • DNA, Complementary / genetics
  • Dermatomyositis / genetics
  • Dermatomyositis / immunology
  • Humans
  • Polymyositis / complications
  • Polymyositis / genetics*
  • Polymyositis / immunology
  • Repressor Proteins / genetics*
  • Repressor Proteins / immunology
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Syndrome

Substances

  • Autoantibodies
  • Autoantigens
  • C1D protein, human
  • Co-Repressor Proteins
  • DNA, Complementary
  • Repressor Proteins