Anti-centromere antibodies are characteristic of the CREST syndrome (Calcinosis, Raynauds, Esophageal dysmotility, Sclerodactyly and Teleangiectasia), version of Systemic Sclerosis (LcSSc). They can also be present in a minority of cases of primary biliary cholangitis (PBC) and Sjogrens syndrome where an SSc overlap syndrome may be present. They are associated with a characteristic fine speckled pattern of staining for anti-nuclear antibodies which is easily seen in cultured cell preparations but readily missed in tissue sections which do not have a high concentration of dividing cells. Under ideal conditions 46 ‘dots’ can be identified per resting cell. On dividing cells the dots appear elongated and aligned along the metaphase plate of the condensed chromatin. This staining is due to binding of antibodies to a number of antigens associated with the centromere. Anti-centromere autoantibodies primarily recognise three centromeric proteins A, B and C or (CENP-A, B and C). A complex relationship exists between the three polypeptides, with CENP-B sharing epitopes with both CENP-A and CENP-C. It has been shown that all sera containing anti-centromeric antigens (ACA), recognise all three polypeptides, although recognition of CENP-B is weak in some instances.
Investigation of unexplained Raynauds; suspected limited cutaneous systemic sclerosis/scleroderma (LcSSc); CREST syndrome.
Anti-centromere autoantibodies occur predominantly in the CREST variant of PSS, whereas antibodies to Scl-70 occur mainly in the diffuse form. Anti-centromere autoantibodies are found in 22-55% of patients with PSS, but of these, 60% have some or all features of CREST syndrome. 10-20% of patients with primary biliary cholangitis (PBC) exhibit anti-centromere autoantibodies usually in association with some symptoms of systemic sclerosis, particularly Raynaud’s phenomenon. A minority of patients with Anti-centromere autoantibodies exhibit no systemic symptoms but do have Raynauds.
Serum Separator Tube (SST)
Indirect immunofluorescence (IF) using rapidly dividing HEp2 cells used for detection of detected when anti-nuclear antibodies. Confirmed using Fluorescence enzyme linked immunoassay (Phadia Immunocap 250) using CENP-B antigen. IgG antibodies are detected or systemic sclerosis antibody immunoblotting.
IF positive/negative: Immunocap positive/negative
Assay range notes
IF positive titre 1:80-1:640
3 – 5 days
Immunology The James Cook University Hospital