Clinical and Molecular Features of Anti-CENP-B Autoantibodies

Abstract

Centromeric proteins are the foundation for assembling the kinetochore, a macromolecular complex that is essential for accurate chromosome segregation during mitosis. Anti-centromere antibodies (ACAs) are polyclonal autoantibodies targeting centromeric proteins (CENP-A, CENP-B, CENP-C), predominantly CENP-B, and are highly associated with rheumatologic disease (lcSSc/CREST syndrome). CENP-B autoantibodies have also been reported in cancer patients without symptoms of rheumatologic disease. The rise of oncoimmunotherapy stimulates inquiry into how and why anti-CENP-B autoantibodies are formed. In this review, we describe the clinical correlations between anti-CENP-B autoantibodies, rheumatologic disease, and cancer; the molecular features of CENP-B; possible explanations for autoantigenicity; and, finally, a possible mechanism for induction of autoantibody formation.

The peptide link between pathogens and human centromere proteins

“…As shown in Figure 2, CENP‐B can be divided into 4 domains and encompasses two primary ACA epitopes. Between the DDE and dimerization domains are two acidic domains composing the mACA2 epitope of CENP‐B 7 . Our analysis indicates most of the abovementioned heptapeptide matches are located at the mACA2 epitope of CENP‐B.…”

“…Between the DDE and dimerization domains are two acidic domains composing the mACA2 epitope of CENP-B. 7 Our analysis indicates most of the abovementioned heptapeptide matches are located at the mACA2 epitope of CENP-B. Besides, other heptapeptide matches have been found to locate at the DDE endonuclease domain or between the DNA binding and DDE domains.…”

“…However, ACA are not specific to SSc. Although with reduced frequency, ACA are detected in multiple additional autoimmune pathologies and malignancies, including primary Sjögren syndrome, 3 systemic lupus erythematosus, 4 rheumatoid arthritis, 5 type 1 diabetes mellitus 6 and breast cancer without symptoms of rheumatologic disease 7 . Subsequent reports identified ACA autoantigens.…”

First electrochemical bioplatforms to determine anti-centromere B antibodies: critical comparison between integrated and magnetic bead-assisted strategies using His-tag chemistry

“…Numerous studies have demonstrated the dysregulation of autoantibodies to intracellular components, such as centromeric proteins, which are the basis for the assembly of the kinetochore, a macromolecular complex essential for the precise segregation of chromosomes during mitosis. 1 Anticentromere antibodies (ACAs), polyclonal autoantibodies directed primarily to three of all the centromeric proteins (CENPA, CENPB and CENPC) 2,3 , are detected in patients with various autoimmune, rheumatologic and cancer diseases. 1 ACAs are considered diagnostic biomarkers in systemic sclerosis (SSc) and are mainly associated with the limited cutaneous subset (lSSc) of this disease which is also known as the CREST syndrome.…”

“…1 Anticentromere antibodies (ACAs), polyclonal autoantibodies directed primarily to three of all the centromeric proteins (CENPA, CENPB and CENPC) 2,3 , are detected in patients with various autoimmune, rheumatologic and cancer diseases. 1 ACAs are considered diagnostic biomarkers in systemic sclerosis (SSc) and are mainly associated with the limited cutaneous subset (lSSc) of this disease which is also known as the CREST syndrome. Deregulation of ACAs has also been reported in systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), rheumatoid arthritis (RA), Sjogren Syndrome (SjS) and Raynaud's phenomenon.…”