Anti-CENPI autoantibodies in scleroderma patients with features of autoimmune liver diseases

Background: Anticentromere autoantibodies have been reported to be associated with scleroderma and serve as a marker in different rheumatic diseases in humans. Major centromere autoantigens described so far include constitutive kinetochore proteins such as CENPA, CENPB, CENPC and CENPH and facultative proteins such as CENPE, CENPF and INCENP. We examined the inner kinetochore component CENPI as a new putative centromere autoantigen in scleroderma patients.

Methods: To test for the presence of CENPI centromere autoantibodies, 72 sera from patients with systemic lupus erythematosus and systemic sclerosis were assayed by immunofluorescence and further tested by immunoblots with an Nt-CENPI recombinant protein.

Results: 8 out of 31 (25.8%) patients diagnosed of scleroderma or Undifferentiated Connective Tissue Disease (UCTD) produced anti-CENPI autoantibodies. Epitopes were demonstrated to be located mainly but not exclusively in the N-terminal domain of the human CENPI protein. Five of the 8 (62.5%) CENPI positive sera also had other autoantibodies related to primary biliary cirrhosis. Further, two patients (25%) with anti-CENPI autoantibodies had concurrent diagnosis of primary biliary cirrhosis.

Conclusions: This study demonstrates that CENPI, a centromere protein that localizes to the inner kinetochore structure, is a human autoantigen. The significance of anti-CENPI autoantibodies could be relevant in scleroderma patients as a marker for concurrent autoimmune liver disease.