Centromere B Antibodies - Scientific Stuff

Nuclear antigens

anti-Centromere antibodies13

ANA: Diffuse speckled nuclear

HLA type association: Non-leucine residue at position 26 of HLA-DQB1 chain

Protein target: Antigens localized at the kinetochore plates

Primary Scleroderma: Centromere protein-B (CENP-B)

Other proteins: CENP-A ; CENP-C

Clinical

Systemic scleroderma, Primary

Sensitivity: 5% to 33%

Specificity: High (99%)

Higher frequency of multisystem involvement

Raynaud’s phenomenon

Xerophthalmia

Peripheral neuropathy (25% vs 2%)

Primary biliary cirrhosis

Less frequent: Anti-SSA or SSB antibodies

Scleroderma variants

CREST (60% to 80%)

Raynaud's: Primary

Other associations

Raynaud’s disease with primary biliary cirrhosis (30%)

Systemic lupus erythematosus (4%)

Mixed connective tissue disease(8%)

Rheumatoid arthritis (1% to 7%)

CENTROMERIC PROTEIN B; CENPB

The structure and function of the centromere regions of mitotic chromosomes have been of interest to cell biologists, geneticists, and rheumatologists. Cell biologists focus on the centromere as both the site of sister chromatid pairing and the site of mitotic spindle attachment. The latter site, the kinetochore, is a trilaminar plaque structure embedded in the chromatin at the surface of the chromosome, as visualized by electron microscopy. Geneticists have been interested in centromeric sequences involved in the control of chromosomal segregation. Rheumatologists became interested in centromere structure when it was observed that centromere compounds are the target of autoimmune responses. Earnshaw et al. (1987) isolated a series of overlapping DNA clones for about 95% of the mRNA that encodes the B centromeric protein. Anticentromere antibodies recognize 3 antigens: CENPA (17 kD; 117139), CENPB (80 kD), and CENPC (140 kD; 117141). CENPB is considered the major centromere antigen, since antibody to it is consistently present at high titer in serum positive for anticentromere antibodies. The B protein is the product of a 2.9-kb mRNA that is encoded by a single locus.