1/34. Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of a patient with progressive systemic sclerosis.A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). methylprednisolone, heparin, and diuretics were administered, without benefit. anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/34. mixed connective tissue disease.Three patients with mixed connective tissue disease (MCTD) had clinical features that included a high incidence of Raynaud phenomenon, arthritis, myositis, and swollen hands. The diagnostic laboratory test result was the presence of high titers of antibody to extractable nuclear antigen. These antibody titers are notably reduced or abolished in patients with MCTD when the tanned red blood cells that are used in the test are pretreated with ribonuclease. Speckled antinuclear antibodies were present in all patients. patients with MCTD have a low incidence of renal disease, are responsive to treatment with prednisone, and have a good prognosis.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
3/34. myositis and interstitial lung disease associated with autoantibody to a transfer rna-related protein Wa.We describe 2 patients with myositis and interstitial lung disease with the autoantibody to Wa antigen, a 48-kDa transfer rna-related protein. In contrast to the previous description of anti-Wa antibody, our patients lacked systemic sclerosis-related features, but had clinical features consistent with those associated with antibodies to aminoacyl-transfer rna synthetases. The difference in clinical presentation between our patients and patients with systemic sclerosis may be explained by recognition of different epitopes on the Wa antigen.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/34. Familial systemic sclerosis following exposure to organic solvents and the possible implication of genetic factors.Both genetic and environmental factors are suspected to play a role in the pathogenesis of systemic sclerosis. We compare its occurrence in 3 sisters working in a dry cleaner's shop and exposed to occupational inhalation of organic solvents. Two sisters showing the human leukocyte antigens (HLA)-DR11/DQ7 haplotype were affected. The third has maintained the same job as the others for over 10 years and has no signs of the disease. The fact that she has a different HLA haplotype points to the significance of genetic factors in increasing the risk of systemic sclerosis. It is suggested that the DR11/DQ7 haplotype enhances the development of a clinical subset of systemic sclerosis associated with production of anti-topoisomerase-I antibodies, and that environmental triggers prime the disease in subjects with this genetic background.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
5/34. Anti-U1RNP antibodies in patients with localized scieroderma.Antibodies to U1 ribonucleoproteins (RNP) have been detected in serum from patients with various autoimmune diseases. However, the presence of anti-U1RNP antibodies in patients with localized scleroderma has not been reported. In this study, we examined the frequency of anti-U1RNP antibodies using immunoprecipitation of U small nuclear RNAs and determined the antigen specificity by immunoblotting. Of 70 serum samples from patients with localized scleroderma, 2 (3%) immunoprecipitated U1 small nuclear rna. Indirect immunofluorescence using HEp-2 cells as substrate showed coarse speckled nuclear fluorescence without nucleolar staining in both of the samples positive for anti-U1RNP antibodies. In addition, the presence of anti-U1RNP antibodies in each serum sample was confirmed by immunodiffusion against HeLa cell extracts. immunoblotting analysis showed anti-70 kDa antibodies in each serum sample. This reaction against 70 kDa protein in the patients with localized scleroderma was analogous to that in patients with systemic sclerosis or mixed connective tissue disease. Both patients with positive serum were diagnosed as having linear scleroderma, but neither had evidence of Raynaud's phenomenon or sclerodactyly. These results indicate that the presence of anti-U1RNP antibodies is one of the serological abnormalities in localized scleroderma, and that the mechanism of induction of anti-U1RNP antibodies in patients with localized scleroderma might be similar to that in patients with systemic sclerosis and mixed connective tissue disease.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
6/34. Development of a CENP-A/CENP-B-specific immune response in a patient with systemic sclerosis.Antibodies directed against an epitope motif on CENP-A have been shown to cross-react with mimotopes on other autoantigens and on Epstein-Barr nuclear antigen 1 (EBNA-1), suggesting a molecular mimicry. We describe here the gradual development of an anticentromere immune response in a patient with systemic sclerosis, which started from an antihistone response and was not mediated by molecular mimicry. Via an epitope on histone H3, the antibody response spread to a homologous epitope in the H3 homology domain of CENP-A. This was followed by an intramolecular epitope spreading to N-terminal peptides of CENP-A containing the known epitope motif G-P-X(1)-R-X(2). From there it spread to corresponding epitopes on CENP-B and to mimotopes of the major CENP-A epitope motif on other autoantigens including EBNA-1. Whether the D-penicillamine treatment received by this patient was involved in the triggering of this cascade remains a matter of speculation.- - - - - - - - - - ranking = 1.5keywords = antigen (Clic here for more details about this article) |
7/34. autoantibodies to NOR 90/hUBF: longterm clinical and serological followup in a patient with limited systemic sclerosis suggests an antigen driven immune response.We describe the clinical and serological followup of a 9-year-old girl with anti-nucleolar organizing region 90/human upstream-binding factor (anti-NOR 90/hUBF) who had features of systemic sclerosis over a period of 17 years, from childhood into adulthood. We review the associations of anti-UBF autoantibodies, and provide evidence that anti-NOR 90/UBF immune response is antigen driven.- - - - - - - - - - ranking = 2.5keywords = antigen (Clic here for more details about this article) |
8/34. Severe ankylosing spondylitis and diffuse systemic sclerosis: case report of a genetic trap.A rare association of ankylosing spondylitis (AS) and systemic sclerosis (SSc) is reported in a Brazilian Mestizo patient presenting a human leucocyte antigen (HLA) genotype that included HLA SSc-susceptibility genes previously reported in different ethnic groups and HLA-B27 associated with AS. The underlying genetic background supporting the full expression of both SSc- and AS-susceptibility alleles and the pertinent literature are discussed.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
9/34. Hypertrophic cardiomyopathy in systemic sclerosis. A report of two cases.We describe two patients with diffuse systemic sclerosis (SSc) where the echocardiogram revealed asymmetric hypertrophy of the interventricular septum with signs of subaortic obstruction consistent with hypertrophic obstructive cardiomyopathy. Hypertrophic cardiomyopathy is associated with the human lymphocyte antigen (HLA DR3), and this may provide a possible link with SSc, as this HLA phenotype is common in the latter condition. However, further studies should examine whether a true association exists.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
10/34. Newly identified U4/U6 snRNP-binding proteins by serum autoantibodies from a patient with systemic sclerosis.We found serum autoantibodies directed against the proteins binding exclusively to U4/U6 of Sm small nuclear ribonucleoprotein particle (snRNP) in serum from a patient (MaS) with systemic sclerosis. Their specificity, called anti-MaS, is distinct from that of known antibodies against U snRNP. The U4 and U6 small nuclear rna from a 32P-labeled HeLa cell extract and five proteins with Mr 150,000, 120,000, 80,000, 36,000, and 34,000, in addition to Sm core proteins (B, B', D, E, F, and G) from an [35S] methionine-labeled extract, were immunoprecipitated by anti-MaS in isotonic solution. However, the Sm core proteins and U4 and U6 small nuclear rna were separated from the protein-A-sepharose facilitated MaS immunoprecipitate by incubation in a solution containing 500 mM NaCl. In immunoblots, anti-MaS antibodies reacted with one protein of Mr 150,000 from a HeLa cell nuclear extract that was fractionated by SDS-PAGE and transferred to a nitrocellulose sheet. The monospecific immunoaffinity purified antibody eluted from the immunoblot band immunoprecipitated U4 and U6 small nuclear rna and reblotted the protein with Mr 150,000. These data indicate that anti-MaS antibodies recognize at least one antigenic protein that binds exclusively to the U4/U6 snRNP.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
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