Centromere autoantibodies

Anticentromere antibodies (ACA) recognise a family of proteins that remain in the centromere region of eukaryotic cells throughout the cell cycle. The three main centromere proteins recognised (CENP-A, CENP-B and CENP-C) localise to separate parts of the centromeric heterochromatin and closely associated kinetochore, and together form targets for a polyclonal autoantibody response. Antibodies to the centromere associated proteins ( CENPs ) are highly useful probes for understanding the mechanisms that regulate higher order chromosome structure and cell division. Full-length clones for the three main CENP antigens have been isolated and Enzyme-linked immunosorbent assay (ELISAs) using recombinant CENP proteins perform well. ACA are most often found in a group of patients with a limited cutaneous form of systemic sclerosis who are predominantly female, and have a relatively favourable outcome apart from a risk of pulmonary hypertension. ACA may occur but are less often found in other autoimmune connective-tissue disorders. Anti-CENP-C antibodies alone may be found in some patients with primary Sjogren's. Anti-CENP-F antibodies have been reported with certain neoplasms. Genetic factors that influence the ACA development include an extended Major Histocompatibility Complex (MHC) gene haplotype. CENP-B and CENP-C generate unique fragments following exposure to granzyme-B that may offer insight into the mechanism of autoantibody generation.