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41.
42.
A hallmark of sera from patients with systemic rheumatic diseases is the presence of circulating autoantibodies directed against nuclear antigens. The identification of the antigens binding to these antibodies has provided the cell biologist and the immunologist with important tools to study cell structure, cell function, and the processes underlying the immune response. Through the elucidation of autoantibody specificities, the clinician has been provided with a better appreciation of the diagnostic and prognostic significance of autoantibodies. Many autoantigens, including those directed against components in the nuclear matrix, chromosomes, Golgi apparatus, and other intracellular antigens, are not yet characterized nor is their clinical significance established. The mechanisms leading to the breakdown of tolerance and the appearance of autoantibodies are not fully understood. Molecular mimicry at an interspecies or an intracellular level may be involved in altering immune tolerance. On the other hand, studies of epitopes on human autoantigens has provided compelling evidence that most autoantibody responses seen in systemic rheumatic diseases are driven by endogenous antigen. 相似文献
43.
Background
Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alstr?m, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. 相似文献44.
Anti‐early endosome antigen 1 autoantibodies were detected in a pemphigus‐like patient but not in the majority of pemphigus diseases
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Kaoru Imaoka Masahiro Ogawa Kwesi Teye Atsunari Tsuchisaka Hiroshi Koga Lars Komorowski Christian Probst Takahisa Hachiya Marvin J. Fritzler Norito Ishii Chika Ohata Minao Furumura Rafal P. Krol Yoshinao Muro Eishin Morita Takashi Hashimoto 《Experimental dermatology》2016,25(5):368-374
Although the major autoantigens in classic pemphigus are desmogleins, sera from various types of pemphigus react with a number of other molecules, including desmocollins and plakin proteins. However, other novel pemphigus‐related autoantigens remain to be identified. In this study, i mmunoblotting for serum from an atypical autoimmune bullous disease patient identified an unknown 175 kDa protein. Subsequent studies using two‐dimensional gel electrophoresis, immunoblotting and mass‐spectrometry identified the 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including indirect immunofluorescence of skin and cultured keratinocytes, two‐dimensional gel electrophoresis and immunoblotting with anti‐EEA1 polyclonal antibody, and preabsorption with EEA1 recombinant protein. Finally, we developed a novel BIOCHIP assay using full‐length EEA1 recombinant protein to detect anti‐EEA1 antibodies. However, none of 35 sera from various types of pemphigus showed anti‐EEA1 antibodies in the BIOCHIP assay, with the exception of the serum from the index case. In addition, various findings in the index case did not suggest pathogenic role of anti‐EEA1 autoantibodies. Therefore, although we successfully identified the 175 kDa protein reacted by a serum of an atypical pemphigus‐like patient as EEA1, novel BIOCHIP study for other pemphigus sera indicated that EEA1 is not a common and pathogenic autoantigen in pemphigus. 相似文献
45.
ASE-1: an autoantigen in systemic lupus erythematosus 总被引:2,自引:0,他引:2
ASE-1 is a 55 kDa nucleolar autoantigen. We show that autoantibodies to this antigen occur at a higher frequency in the sera of patients with SLE than in other systemic rheumatic diseases and that the specificity of ASE-1 as a serum marker of SLE increases as the number of epitopes recognized by the sera increases. Autoantibodies to ASE-1 were temporally associated with autoantibodies to HsEg5 but were not found in conjunction with other known serum markers of SLE. The frequency of antibodies to ASE-1 epitopes in a SLE cohort was approximately the same as anti-dsDNA. However, anti-dsDNA is associated with renal involvement, whereas ASE-1 reactivity shows an association with a history of serositis. We conclude that ASE-1 is correlated with serositis and that ASE-1 should be added to a list of autoantigens that are considered important serological features of SLE. 相似文献
46.
Miyachi K Hosaka H Nakamura N Miyakawa H Mimori T Shibata M Matsushima S Chinoh H Horigome T Hankins RW Zhang M Fritzler MJ 《Scandinavian journal of immunology》2006,63(5):376-382
We previously reported that 12.5% of primary biliary cirrhosis (PBC) sera reacted with a 95 kDa cytosol protein (p95c) that was subsequently identified as a p97/valosin-containing protein (VCP). The clinical features and course of the six anti-p97/VCP-positive PBC patients with Scheuer's stage 1 and 2 liver biopsies were monitored for an average of 15 years. This group was compared with 50 PBC patients that did not have detectable anti-VCP. Autoantibodies to a full-length recombinant p97/VCP were assayed by immunoprecipitation. All six PBC patients with anti-VCP had antibodies to the mitochondrial pyruvate dehydrogenase complex-E2 antigen as measured by an addressable laser bead immunoassay. The first was a male with no evidence of liver failure that died of cerebral infarction at the age of 85. The second was a 73-year-old female with Hashimoto's thyroiditis who has remained clinically stable without ursodeoxycolic acid (UDCA) treatment. Although the third had no HCV antibodies, he developed hepatocellular carcinoma at the age of 76 and died of renal failure at 78. The fourth was a 50-year-old female who remained clinically stable during follow-up and the fifth with Hashimoto's thyroiditis and stable liver function following UCDA treatment. The sixth was a male patient presenting a mild clinical course. The clinical course of these patients was in contrast to the 50 comparison group PBC patients who did not have anti-p97/VCP. As the six PBC patients with anti-p97/VCP antibodies had slowly progressive liver disease and no mortality related to autoimmune liver disease, our observations suggest that this autoantibody might be an indicator of a favourable prognosis. 相似文献
47.
Hudson M Walker JG Fritzler M Taillefer S Baron M 《The Journal of rheumatology》2007,34(11):2218-2223
OBJECTIVE: Although complement fixation is not commonly thought to be part of the pathogenesis of systemic sclerosis (SSc), hypocomplementemia has been associated with SSc. We hypothesized that hypocomplementemia in SSc might indicate the presence of overlap disease. We investigated if SSc patients with hypocomplementemia had more features of overlap disease than those with normal complement levels. METHODS: Study subjects consisted of those enrolled in the Canadian Scleroderma Research Group Registry. Patients were divided into 2 groups: those with normal complement levels (normal C3 and C4) and those with hypocomplementemia (low C3 or C4). Evidence of overlap disease was defined as physician reports of other specific rheumatic conditions. Autoantibodies were assayed. Differences in rates of concomitant diseases and in antibody profiles were compared between groups. RESULTS: Our study included 321 patients (88% women, mean age 56 +/- 13 yrs, mean disease duration 11 +/- 9 yrs). Of these, 276 (86%) had normal complements and 45 (14%) had hypocomplementemia. Patients with hypocomplementemia were significantly more likely to have physician-reported inflammatory myositis (27% vs 12%; p < 0.008) and vasculitis (11% vs 2%; p < 0.011) than those with normal complement. There was also a trend toward more antichromatin antibodies (18% vs 9%; p = 0.051) in patients with hypocomplementemia compared to normals. CONCLUSION: Hypocomplementemia may identify a particular subgroup of SSc patients who have overlap disease. 相似文献
48.
Fritzler MJ 《Lupus》2006,15(7):422-427
There is a rapid proliferation of new technologies to identify an ever increasing spectrum of autoantibodies in diverse medical conditions that range from organ-specific autoimmune diseases to systemic rheumatic diseases. Although many laboratories have adopted diagnostic platforms, such as enzyme linked immunoassays (ELISAs), to improve turn around times and meet budget constraints, the prevailing evidence is that the rapid adoption of new technologies is not attended by an appropriate balance of assay sensitivity and specificity. Emerging diagnostic technologies include addressable laser bead immunoassays, microarrays in microfluidics platforms and nanobarcode particles. Although these technologies provide advantages of high-throughput, multiplexed autoantibody assays that can be coupled to other disease specific biomarkers (ie, cytokines, single nucleotide polymorphisms) there is a clear need for standardization and internal validation before they are adopted into the clinical diagnostic laboratory. 相似文献
49.
Miyachi K Hirano Y Horigome T Mimori T Miyakawa H Onozuka Y Shibata M Hirakata M Suwa A Hosaka H Matsushima S Komatsu T Matsushima H Hankins RW Fritzler MJ 《Clinical and experimental immunology》2004,136(3):568-573
We have reported previously that p95c, a novel 95-kDa cytosolic protein, was the target of autoantibodies in sera of patients with autoimmune hepatic diseases. We studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein from [(35)S]-methionine-labelled HeLa lysates and had a specific precipitin band in immunodiffusion. Thirteen sera were available to test the ability of p95c antibodies to inhibit nuclear envelope assembly in an in vitro assay in which confocal fluorescence microscopy was also used to identify the stages at which nuclear assembly was inhibited. The percentage inhibition of nuclear envelope assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and the swelling of nucleus was inhibited at several stages. The percentage inhibition of nuclear assembly was correlated with the titre of anti-p95c as determined by immunodiffusion. To confirm the identity of this autoantigen, we used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a radiolabelled recombinant protein that was then used in an immunoprecipitation (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97 have similar molecular masses and cell localization, and because the majority of sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly, this is compelling evidence that p95c and p97/VCP are identical. 相似文献
50.
Humoral immune response in patients with hemophilia 总被引:1,自引:0,他引:1
D S Matheson B J Green M J Fritzler M C Poon T J Bowen D I Hoar 《Clinical immunology and immunopathology》1987,44(1):41-50
Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses. 相似文献