Diversity of antinuclear antibodies in progressive systemic sclerosis

Tan, Eng M.; Rodnan, Gerald P.; García, Ignacio Hernández; Möroi, Y; Fritzler, Marvin J.; Peebles, Carol

doi:10.1002/art.1780230602

Cited by 477 publications

(81 citation statements)

References 14 publications

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“…Twenty-six patients with RP (one man, 25 women, mean age 42·3 Ϯ 15·3 years, mean duration of RP 10·4 Ϯ 9·9 years) were studied. Sixteen patients had idiopathic RP, 10 had RP with positive autoantibodies: four with anti-nuclear, two with anti-nucleolar, and four with anticentromere antibodies, as assessed by indirect immunofluorescence on rat liver and on the HEp2 cell line [21]. No patient had positive Scl 70 antibodies, as assessed by counterimmunoelectrophoresis, using rabbit thymus extract and human spleen extract as antigen [22].…”

Section: Patientsmentioning

confidence: 99%

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

Molteni

Bella

Mascagni

et al. 1999

Clinical and Experimental Immunology

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SUMMARYThe aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-g compared with healthy controls. However, patients with clinically active disease had lower IFN-g levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-g than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4 þ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-g. We suggest that T lymphocytes producing high levels of IFN-g might play a protective role in RP patients and in established scleroderma.

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Section: Patientsmentioning

confidence: 99%

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

Molteni

Bella

Mascagni

et al. 1999

Clinical and Experimental Immunology

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“…Apart from the reported antibodies to nucleolar RNPs and laminar proteins in single scleroderma sera (10,11), three types of autoantibodies have been suggested to be associated specifically with progressive systemic sclerosis: (a) antibody to centromere/kinetochore, reported to be a marker antibody for the Calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) variant (12,13); (b) antibody to a basic, labile, chromatine-associated, nonhistone 70,000-mol wt nuclear protein (Scl-70) (14,15); and (c) antinucleolar antibody ( 16), which might be specific for scleroderma or diseases with scleroderma overlap features.…”

Section: Introductionmentioning

confidence: 99%

Scl-86, a marker antigen for diffuse scleroderma.

Venrooij¹,

Stapel²,

Houben³

et al. 1985

J. Clin. Invest.

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More than 300 sera from patients with a connective tissue disease were analyzed with the immunoblotting technique. The presence of autoantibodies against an 86,000-mol wt marker antigen for diffuse scleroderma (Scl-86) was found in 14 out of 33 patients with scleroderma. The presence of anti-Scl-86 antibodies seemed to correlate with the diagnosis of diffuse scleroderma since they were found in 13 out of 22 diffuse scleroderma patients and in only one out of 11 patients with limited scleroderma. All scleroderma sera (33 patients' sera and 13 reference sera) were also tested for the presence of anti-Scl-70 antibodies. It was found that all anti-Scl-70 positive sera (n = 25) contained anti-Scl-86 antibody as well, suggesting a relationship between these two antigens. However, the Scl-86 antigen was shown to be an extremely insoluble nonchromosomal protein, resistant to boiling in sodium dodecyl sulfate. This contrasts with the Scl-70 antigen, which has been described as a thermolabile, soluble antigen present in the chromatin fraction. Together, our results are consistent with the idea that Scl-70 is a degradation product of Scl-86.The Scl-86 antigen is present in freshly prepared rabbit thymus, spleen, and liver nuclei as well as in nuclei from various cultured cell lines, but is not detectable in extractable nuclear antigen from rabbit thymus.In a limited retrospective study, the anti-Scl-86 antibodies were found in two sera from patients with Raynaud's phenomenon before the development of diffuse scleroderma. Therefore, it is possible that screening of patients' serum for this antibody might predict the development of diffuse scleroderma.

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“…High titers of antibodies to n-RNP, a complex of RNA and protein, is often associated with mixed connective tissue disease (18). Sm, a protein antigen, is found only in SLE (2) while a 70,000-mol wt nuclear protein, Scl-70, has been found to be highly specific for progressive systemic sclerosis (23). Recently, an antigen termed Ku, which was characterized as being a 300,000-mol wt acidic nuclear protein, was found to be a marker for patients with polymyositis-scleroderma overlap (5).…”

Section: Discussionmentioning

confidence: 99%

Diversity of autoantibodies in avian scleroderma. An inherited fibrotic disease of White Leghorn chickens.

Haynes¹,

Gershwin²

1984

J. Clin. Invest.

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Abstract. University of California, Davis line 200 White Leghorn chickens develop an inherited progressive fibrotic disease that includes the appearance of antinuclear antibodies (ANA). To further characterize these ANA, serial aged line 200 birds were studied. Greater than 50% of line 200 birds develop antinuclear and anticytoplasmic antibodies; fluorescent staining patterns included cytoplasmic spider web, most prevalent at 1 mo of age, and fine speckled patterns, characteristic of chickens 6 mo and older. By enzyme-linked immunosorbent assay, 40.4% of line 200 birds were found to have antibodies to single-stranded DNA (ssDNA). In contrast, antibodies to histones, RNA, or poly A * poly U were not detected. Precipitating antibodies to saline extracts from chicken liver were noted in 33.3% ofline 200 birds. Saline extracts from turkey, pheasant, and partridge liver but not rat, rabbit, or mouse tissues were also positive in immunodiffusion testing with these line 200 birds. The antigenicity of chicken liver extracts was sensitive to pronase, protease K, and pH variations >10 and <5; however, they were resistant to trypsin, DNase, RNase, and incubation at 370C and 560C for 1 h. Cell fractionation in conjunction with column chromatographic techniques revealed that several protein antigens with apparent molecular weights in the range of 62,000-290,000 were present in cytoplasm but not in isolated nuclei. Line 200 sera were not reactive against nuclear ribonucleoprotein, Sm, Scl-70, or SS-B/La antigens. Thus, line 200 chickens develop antinuclear and anticytoplasmic antibodies at an

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Diversity of antinuclear antibodies in progressive systemic sclerosis

Cited by 477 publications

References 14 publications

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

Scl-86, a marker antigen for diffuse scleroderma.

Diversity of autoantibodies in avian scleroderma. An inherited fibrotic disease of White Leghorn chickens.

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