Anti-centromere antibodies (ACA)

  title={Anti-centromere antibodies (ACA)},
  author={Cornelis Kallenberg},
  journal={Clinical Rheumatology},
  • C. Kallenberg
  • Published 1 March 1990
  • Medicine, Biology
  • Clinical Rheumatology
ConclusionACA are directed towards centromeric proteins (CENP) with M.W. of 17 KD (CENP-A), 80 KD (CENP-B) and 140 KD (CENP-C). At least 6 epitopes on these proteins are recognized by ACA, but CENP-B (that has been partially cloned) seems to be the primary autoantigen. ACA are clinically associated with the CREST syndrome or limited cutaneous systemic sclerosis (prevalence ±55%), and are also found in 30% of patients with primary biliary cirrhosis (who demonstrate additionally symptoms of CREST… 

Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis

ACA displays a specific ANA staining pattern with a bimodal distribution, and ACA-positive RA may constitute a distinct subset with specific clinical features.

Loss of BRCA1 impairs centromeric cohesion and triggers chromosomal instability

A novel role of BRCA1 is uncovered in maintaining chromosomal stability through its contribution to the mitotic centromere integrity necessary for faithful segregation of sister‐chromatids during cell division.

Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung dysfunction

Serum level of IGFBP-2 was significantly increased in SSc patients compared to HS, and negatively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO) at 2-year follow-up, showing for the first time that serum levels of IGF BP-2 might be a prognostic factor of the development of SSc-ILD.

An easy prediction rule for diffuse cutaneous systemic sclerosis using only the timing and type of first symptoms and auto-antibodies: derivation and validation.

A simple prediction rule was designed to attribute a low/high risk category for development of dcSSc and is suited for assigning intensified screening at the time of initial diagnosis of SSc to patients most at risk for dcS sc.

Serum IGFBP-2 in Systemic Sclerosis as a Protective Factor of Lung Dysfunction

It is shown for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD, a rare connective tissue disease associated with rapid evolving interstitial lung disease and may be a prognostic factor of alveolo-capillary dysfunction.

Biomarkers in systemic sclerosis.

There is an unmet need for validated biomarkers for diagnosis, disease classification, and evaluation of organ involvement and therapeutic response in systemic sclerosis.

Targeting cell cycle checkpoints to specifically kill cancer

Identifying checkpoints that are commonly lost in a wide rangen of tumour cells and developing chemotherapeutics that selectively target these lost checkpoints may provide a means of producing more potent anti-cancer drugs that have few side effects than current treatments.

Chemical dissection of the cell cycle: probes for cell biology and anti-cancer drug development

A novel cancer cell-based high-throughput chemical screen for cell cycle modulators identified novel G1, S, G2, and M-phase specific inhibitors with drug-like properties and diverse chemotypes likely targeting a broad array of processes.



Autoantibody to centromere (kinetochore) in scleroderma sera.

The autoantibody was present in high frequency in the calcinosis/Raynaud's phenomenon/esophageal dysmotility/sclerodactyly/telangiectasia variant of scleroderma and appeared to be a protein or polypeptide tightly bound to DNA.

Analysis of anticentromere autoantibodies using cloned autoantigen CENP-B.

A radioimmunoassay based on cloned CENP-B has demonstrated that sera from greater than or equal to 96% of patients with ACA recognize the cloned antigen, thus defining a region of the protein that is recognized by virtually all patients withACA.

Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma

Examination of “preimmune” serum samples from a patient who progressively developed the symptoms of scleroderma CREST over a period of several years shows that these patients make antibody species recognizing at least three distinct epitopes on C ENP-B and two on CENP-C.

High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients.

It was possible to show, by three independent criteria, that Scl-70 is the abundant nuclear enzyme DNA topoisomerase I, and antibody probes of high titer and high affinity are now available for the study of this important nuclear enzyme.

Detection of anticentromere antibodies using cloned autoantigen CENP-B.

A solid-phase enzyme-linked immunosorbent assay has been established using a cloned fusion protein, CtermCENP-B [beta-gal], as antigen, which was more sensitive than immunofluorescence techniques in detecting anticentromere antibodies in patients with scleroderma or Raynaud's disease.

Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies.

The ACA response is highly uniform in the patient population, and antibody to CENP-B shows a 100% correlation with anti-centromere staining by indirect immunofluorescence.

Human anti-centromere sera recognise a 19.5 kD non-histone chromosomal protein from HeLa cells.

Immunoblotting experiments with a protein fraction enriched in HeLa chromosomal proteins revealed that the antigenic target common to all 18 sera is a polypeptide of 19.5 kD, which is not one of the core histones, and is not soluble under conditions which favour the release of nuclear ribonucleoprotein particles.

Clinical associations of anticentromere antibodies and antibodies to topoisomerase I. A study of 355 patients.

Anticentromere antibodies and anti-topoisomerase I were found primarily in patients with scleroderma, CREST syndrome, and Raynaud's phenomenon, whereas anti- topo I identified patients with skin and cardiac involvement and patients with malignancies.

Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome.

Three types of antibodies appeared to be highly specific for scleroderma: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody, and the anti-centromere antibody appeared to been highly selective for the CREST variant of progressive systemic sclerosis.