Autoantibody to centromere (kinetochore) in scleroderma sera.

Abstract

Sera from patients with scleroderma contained several autoantibodies to nuclear antigens which were distinguished by different patterns of nuclear immunofluorescence staining. One of these autoantibodies reacted with centromeric regions of chromosomes. In chromosome spreads, the staining appeared as two small spheres at the centromere, resembling kinetochores. The antigenic determinant appeared to be a protein or polypeptide tightly bound to DNA. The autoantibody was reactive with centromeres of cells derived from humans, mice, and Chinese hamsters. The autoantibody was present in high frequency in the calcinosis/Raynaud's phenomenon/ esophageal dysmotility/sclerodactyly/telangiectasia variant (CREST) of scleroderma.Progressive systemic sclerosis, also known as scleroderma, is a chronic systemic rheumatic disease that can affect many organ systems including the skin and subcutaneous tissues, the gastrointestinal tract, the heart, the lungs, and the kidneys. The etiology of the disease is unknown but much information has been accumulated on the clinical, pathogenetic, and serological abnormalities associated with it. Sera of patients with scleroderma have been shown to contain autoantibodies to nucleolar and other intranuclear components. Generally, these autoantibodies have been detected by the immunofluorescence technique. By using tissue sections as substrate, autoantibodies have demonstrated different patterns of nuclear staining which have been described variously as nucleolar, speckled, and homogeneous (1, 2).Some of the intranuclear antigens reacting with autoantibodies in scleroderma sera have been elucidated. There is a 4S-6S RNA, isolated from liver nucleoli, that specifically precipitates with serum autoantibody (3). Recently, another nuclear antigen has been identified and termed . This was shown to be a nonhistone nuclear protein of approximately 70,000 daltons. By polyacrylamide gel electrophoresis, Scl-70 was identified as a distinct protein band closely associated with but clearly separable from histone fraction H1.In this report, we describe an autoantibody in scleroderma sera which reacts with the centromere (kinetochore) of chromosomes. This autoantibody was initially observed to give speckled nuclear staining on substrates consisting of organ sections. When tissue culture cells of different origins were used as substrates, the speckled staining was clearly observed to be associated with the centromeres of chromosomes. Further analysis suggested that the centromere antigen might be protein or polypeptide components tightly bound to the centromeric DNA of chromosomes.MATERIALS AND METHODS Serum. Sera from 32 patients with scleroderma (25 females and 7 males) were studied. Twenty-three healthy persons (15 females and 8 males) were used as controls. All sera were heat-inactivated at 56°C for 30 min prior to use.Immunofluorescence Studies. The indirect fluorescent antibody technique (5) was used to determine the nuclear staining patterns produced by the sera under study. The substrates cons...

HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint

“…Specific expression of HBx protein in ChangX and SNU368 cells but not in Huh7 and Chang cells were shown (Figure 2c). We first confirmed that BubR1 in SNU368 cells co-localized at the kinetochores of the condensed chromosomes with the kinetochore-specific marker, CREST (Moroi et al, 1980; data not shown). Notably, a portion of the HBx protein co-localized with hBubR1 at the kinetochores in SNU368 cells as well as in ChangX cells (Figure 2a …”

Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis

“…The ACA patients were older at the onset of their first symptom attributable to PSS: mean age 44. 4 versus 39.2 years (P < 0.01). As expected from this age difference, 50% of the women with ACA were postmenopausal at the onset of their symptoms compared with only 26% of the women without ACA.…”

Antinuclear Antibodies in Localized Scleroderma

“…In progressive systemic sclerosis, 3 types of antibodies appeared to be highly specific: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody (17,18). Antibodies to nRNP were also occasionally detected.…”